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Frontiers in Pediatrics ·

Volume 14 - 2026 | https://doi.org/10.3389/fped.2026.1939494

The pathogenic role of high-titer anti-Ro52 antibodies in neonatal lupus erythematosus: insights from a 9 case series

  • Shuo Cheng1,2
  • Yi Jiang1
  • Suo Zhang1
  • Jiaming Huang1
  • Xiaoxue Wang1
  • Huanyu Xie1,2
  • Meiying Wang1,2*corresponding author
  1. 1Department of Rheumatology and Immunology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
  2. 2Shenzhen University Medical School, Shenzhen University, Shenzhen, China
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Abstract

Neonatal Lupus Erythematosus (NLE) is a rare acquired autoimmune disease caused by the transplacental transfer of maternal anti-Ro/SSA and anti-La/SSB antibodies. Despite the high prevalence of these antibodies in mothers with Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SS), the clinical manifestations in neonates are highly heterogeneous, ranging from transient cutaneous lesions to life-threatening congenital heart block (CHB). This study analyzed a case series of nine mother-infant pairs diagnosed with NLE. We integrated clinical outcomes, maternal serological profiles (including quantitative anti-Ro52, Ro60, and La titers), and pharmacological interventions to explore the determinants of disease severity and organ-specific manifestations. Among the nine mothers, six (66.7%) had Sjögren's syndrome and three (33.3%) had systemic lupus erythematosus, including two with secondary antiphospholipid syndrome. Notably, 88.9% of mothers were diagnosed with autoimmune disease during or after the affected pregnancy. All mothers demonstrated antinuclear antibody positivity and were uniformly positive for anti-SSA/Ro, anti-SSB/La, and anti-Ro52 antibodies. Cardiac involvement occurred in three pregnancies, including recurrent complete CHB leading to pregnancy termination in one mother. One fetus with second-degree atrioventricular block received prompt dexamethasone therapy and achieved successful reversal of conduction abnormalities. Cutaneous manifestations were observed in five neonates, while hematologic involvement, primarily thrombocytopenia and anemia, occurred in four cases. Maternal hypocomplementemia and elevated inflammatory markers appeared to be associated with more severe fetal outcomes. All nine mothers (100%) tested positive for high-titer anti-Ro52 antibodies, a finding consistent with the proposed role of anti-Ro52 as a risk biomarker for NLE. Intensive fetal echocardiographic surveillance between 16 and 26 weeks of gestation is vital to capture the critical window of low-degree conduction block, where synergistic immunomodulation with dexamethasone can reverse fetal heart block prior to irreversible nodal fibrosis. NLE serves as an early warning sign of occult maternal autoimmune disease, requiring long-term maternal follow-up.

Keywords

1 Introduction

Neonatal Lupus Erythematosus (NLE) is a rare autoimmune syndrome resulting from the transplacental transfer of maternal autoantibodies to the fetus (1), associated with the presence of maternal anti-Ro/SS-A and anti-La/SS-B antibodies. Despite the high prevalence of anti-Ro/SSA and anti-La/SSB antibodies in patients with Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SS), the vast majority 98% of infants born to antibody-positive mothers remain free of severe complications such as cardiac conduction block (2), the incidence of NLE in susceptible pregnancies is approximately 2% (3). However, the recurrence risk rises significantly to 17%–20% for mothers with a history of a child affected by Congenital Heart Block (CHB) (4). Furthermore, NLE is the primary etiology of neonatal CHB, accounting for 80%–95% of cases diagnosed within the first 28 days of life (5, 6). Aside from cardiac manifestations, skin lesions are common in NLE, and the rate of skin involvement varies among different ethnic groups, with up to 80% of NLE patients in Asia having skin involvement (7, 8). The rash of neonatal lupus presents as transient annular erythematous scaling lesions on the face, scalp, trunk, and limbs, with histopathology demonstrating granular IgG deposition and vesicular changes at the dermal-epidermal junction and skin appendages (9). The rash usually appears after birth and is typically caused by sun exposure (10, 11), it has also been reported to correlate with anti-U1RNP antibodies in certain contexts (12). Interestingly, the clearance of these cutaneous manifestations closely mirrors the clearance of maternal anti-SSA/Ro antibodies from the infant's circulation (8). While historical research indicates that mothers of infants with NLE generally exhibit positivity for anti-SSA/Ro, anti-SSB/La, or anti-U1RNP antibodies (2), our study uniquely expands upon these observations by identifying anti-Ro52 antibodies as a distinct and highly uniform immunological signature within our cohort. Beyond these dermatological features, other transient systemic manifestations, including hepatobiliary disease and hematologic disorders, may manifest postpartum (13).

Our case study shows that mothers of neonatal lupus share common antibody characteristics, which can also affect the infant's heart, blood, skin, and other systems. We constructively present a case of a child with successfully reversed CHB, thus comprehensively reporting on NLE and gaining more potential experience for clinical work.

2 Methods

This retrospective, single-center case series was conducted at The First Affiliated Hospital of Shenzhen University between 2019 and 2025. Electronic medical records were systematically reviewed to identify mother-infant pairs affected by NLE. Antinuclear antibodies were detected by indirect immunofluorescence, and titers and patterns were recorded. Anti-Ro52 antibodies were quantified by enzyme-linked immunosorbent assay; results are expressed as the ratio of the sample optical density to the cut-off value (S/C.O.), with a ratio ≥1.0 considered positive. Anti-SSA/Ro, anti-SSB/La, anticardiolipin IgG, and anti-β2 glycoprotein I IgG antibodies were measured by the routine clinical laboratory assays used at our institution. Serum C3 and C4 were quantified by standard clinical laboratory methods and are expressed in g/L.

Patients were eligible if they had an NLE diagnosis established by a rheumatologist based on American College of Rheumatology criteria (14). Exclusion criteria comprised: (1) major congenital malformations, chromosomal anomalies, or inherited metabolic disorders; (2) critical data missingness that risked confounding results; and (3) lack of parental consent. The investigation protocol was conformed with the Helsinki Declaration and approved by the Ethics Committee of The First Affiliated Hospital of Shenzhen University.

Patient data were retrieved from electronic medical records. Extracted parameters included baseline perinatal demographics, familial/maternal autoimmune and allergic background, clinical presentations, laboratory profiles.

3 Presentation of cases

This study included nine mothers aged 28 to 38 years, who presented diverse histories of autoimmune diseases. Notably, SS dominated maternal diagnosis, consistent with literature reports that approximately 50% to 90% of mothers with NLE have SS or are in a subclinical state (13, 15).

3.1 Maternal demographic and clinical characteristics

Table 1 summarizes the demographic, clinical, and serological characteristics of the nine mothers included in this study. All mothers had a confirmed history of underlying autoimmune diseases. SS was the most prevalent diagnosis, observed in 6 of the 9 cases (66.7%). The remaining 3 patients (33.3%) were diagnosed with SLE, among whom two were concomitantly diagnosed with Antiphospholipid Syndrome (APS). In this cohort, 88.9% (8/9) of the mothers were diagnosed with autoimmune disease during or after this abnormal pregnancy. This underscores the absolute necessity for obstetricians to screen mothers for ANA and ENA profiles when encountering fetal arrhythmias or recurrent miscarriage.

Table 1. Demographic and clinical characteristics for mother.

CaseANAKaryotypeSSASSBRo-52CL IgGβ2GP1 IgGC3 (g/L)C4 (g/L)DiagnosisAge at deliveryAge at diagnosis
11:3,200Speckled/Nucleolar2.633.343.75001.480.18SS2626
21:320Speckled1.953.432.041.92.11.290.269SS3131
31:1,000Speckled2.260.863.141.952.920.830.14SS2727
41:10,000Homogeneous/Cytoplasmic1.912.423.432.1<20.870.173SS3032
51:3,200Speckled/Nucleolar0.712.012.82.523.360.860.194SLE3128
61:1,000Unknow+++++++++80.814.20.910.113SLE/APS2929
71:1,000Speckled1.942.032.651,2881,8400.850.119SLE/APS2525
81:1,000Speckled2.571.812.4322.3300.970.288SS/APS2930
91:320Speckled2.071.453.954.22.51.020.106SS3737

Immunological and serological evaluations revealed profound autoantibody reactivity in all subjects. As shown in Table 1, antinuclear antibodies (ANA) were universally positive (9/9, 100%), with titers ranging from 1:320 to 1:10,000. The speckled pattern was the predominant ANA karyotype. Notably, in contrast to previous studies reporting variable frequencies of anti-SSA/Ro, anti-SSB/La, and anti-Ro52 antibodies, all nine mothers in our cohort exhibited a remarkably uniform autoantibody profile, demonstrating triple positivity for anti-SSA/Ro, anti-SSB/La, and anti-Ro52 antibodies.

Antiphospholipid antibody screening showed that anticardiolipin (aCL) IgG and anti-β2 glycoprotein I (β2GP1) IgG levels were markedly elevated in the two patients with SLE and secondary APS (Cases 6 and 7), and mildly elevated in one SS patient (Case 8). Furthermore, serum complement levels varied among the cohort; borderline low or decreased levels of C3 and C4 were observed predominantly in patients with SLE/APS, reflecting potential complement consumption related to disease activity.

3.2 Cardiac manifestations of neonatal lupus

Cardiac involvement represented the most severe manifestation of NLE in this cohort, occurring in three pregnancies across two mothers (Cases 1, 2, and 9), all of whom carried high-titer anti-Ro-52 antibodies.

As shown in Table 2, Case 1 experienced two consecutive pregnancy losses attributable to fetal cardiac conduction block. During the first pregnancy, fetal echocardiography at approximately 16 weeks of gestation revealed a severe cardiac conduction block, resulting in an elective termination. Following a diagnosis of SS and the initiation of hydroxychloroquine, prednisone, and aspirin, the patient conceived again. At 20 weeks of gestation during her second pregnancy, fetal echocardiography confirmed a complete third-degree atrioventricular block complicated by severe fetal heart failure. Despite aggressive intervention with dexamethasoneand intravenous immunoglobulin (IVIG), fetal cardiac function could not be salvaged, necessitating a second termination. These outcomes underscore the irreversibility of CHB once fibrosis and calcification of the atrioventricular node are established. Case 2 whose SS diagnosis was incidentally prompted by the discovery of the fetal cardiac abnormality itself, presented with second-degree AVB detected at 26 weeks of gestation during routine monitoring. The rapid progression of the fetal cardiac lesion necessitated the termination of the pregnancy.

Table 2. Comprehensive maternal-fetal clinical characteristics and outcomes of the NLE case series.

CaseNeonatalMaternalFinal outcome
Cardiac involvementCutaneous manifestationsHematological findingsInflammatory & immunological markersGestational age
12nd/3rd-degree AV block, severe heart failureNoneAnemia (Hb 89 g/L)Elevated CRP (27.04 mg/L)High IgG (23.56 g/L)20 weeksFetal demise
22nd-degree AV blockNoneNormalStable22 weeksFetal demise
3NoneAnnular facial erythemaAnemia (Hb 116 g/L)Stable8 weeksLive birth
4NoneGeneralized rashNormalStable6 weeksLive birth
5NoneFacial erythemaNormalStable19 weeksLive birth
6NoneGeneralized rashAnemia (Hb 102 g/L)Elevated ESR (45 mm/h)22 weeksLive birth
7NoneFacial and chest erythemaAnemia (Hb 110 g/L)Leukopenia (WBC 3.5 × 109/L)Stable6 weeksLive birth
8NoneNoneNormalStable22 weeksLive birth
92nd-degree AV blockNoneAnemia (Hb 101 g/L)Hypocomplementemia (Low C4: 0.106 g/L)22 weeksOngoing

Case 9 provided the most instructive example of timely cardiac intervention in this cohort. At 22 weeks of gestation, intensive fetal echocardiographic surveillance detected the emergence of second-degree AVB. Recognizing this as a pathophysiological inflection point prior to irreversible atrioventricular nodal fibrosis, the clinical team promptly added dexamethasone (4 mg/day) to her existing regimen of aspirin and hydroxychloroquine.

3.3 Cutaneous involvement of NLE

Cutaneous involvement was the most frequently observed clinical manifestation among the live-born infants in Table 2, unambiguously identified in 5 cases (Cases 3, 4, 5, 6, and 7). The clinical presentation predominantly involved the facial region, though the extent of the lesions varied among the affected neonates.

According to the clinical data, Cases 3 and 5 presented primarily with isolated facial rashes. These typically manifest as classic periorbital erythema and annular erythematous plaques. Case 7 exhibited a more widespread dermatological phenotype, characterized by multiple red erythematous lesions distributed across both the facial region and the trunk. Cases 4 and 6 also presented with distinct neonatal rashes consistent with the NLE cutaneous profile. Morphologically, the typical NLE rash presents as annular or oval red patches with slightly raised edges and a central clearing, predominantly affecting sun-exposed areas such as the periorbital region, scalp, and trunk. These lesions typically emerge within the first few weeks of life and are highly photosensitive, often triggered or exacerbated by ultraviolet radiation exposure.

3.4 Hematologic involvement of NLE

Case 8 of neonatal thrombocytopenia highlighted hematologic involvement, with the infant's platelet count plummeting to 30 × 109/L on the second day after birth. This is a typical hematologic presentation of NLE (16), due to increased platelet destruction caused by cross-reaction or immune complex formation between anti-Ro/La antibodies and fetal platelet antigens (17). Such thrombocytopenia is usually self-limiting, but if the titer is too low (<50), there is a risk of intracranial hemorrhage, requiring consideration of intravenous immunoglobulin (IVIG) intervention. In addition, several infants (cases 1, 3, 6, 7 and 9) had varying degrees of anemia, reflecting a temporary suppression of the bone marrow hematopoietic system.

3.5 The influence of maternal blood indicators on postpartum outcomes

The systemic inflammatory and immunologic burden of the mother directly dictates the severity of the placental and fetal microenvironment.

As shown in Table 2, case 1 had significantly elevated CRP (27.04 mg/L) and the lowest hemoglobin level (89 g/L), consistent with its worst pregnancy outcome. High inflammation levels may indicate high pathogenicity of antibodies or severe placental inflammation. Case 6 had an ESR of 45 mm/h, suggesting active SLE. Case 4, despite extremely high titers, had normal CRP and ESR, but high albumin levels (46.7 g/L), which may explain why the fetus had intact cardiac function despite the rash, suggesting that a lower overall maternal inflammatory burden provided some protection to the fetus.

Most patients had normal liver and kidney function, but weakly positive urine protein was observed in cases 1 and 3, which may suggest underlying mild lupus nephritis or renal burden during pregnancy. Complement consumption proved to be another critical biomarker. Serum complement levels varied among the cohort, with borderline low or significantly decreased levels of C3 and C4 observed predominantly in the patients diagnosed with SLE and secondary APS, reflecting profound complement activation and consumption related to disease activity at the maternal-fetal interface. Most alarmingly, Complement C4 reached its absolute nadir in Case 9 (0.106 g/L), a depletion that aligned with exquisite precision with the emergence of fetal cardiac conduction abnormalities. The activation of the complement system serves as a massive amplifier of tissue damage in NLE, and severe hypocomplementemia typically reflects the substantial tissue deposition and depletion of circulating immune complexes.

4 Discussion

Neonatal lupus is a classic model of passively acquired autoimmune disease, in which maternal IgG autoantibodies against the Ro/La ribonucleoprotein complex cross the placenta and target fetal tissues, causing immune-mediated damage to multiple target organs in the fetus and newborn (13, 18, 19). The clinical phenotypes of NLE are highly heterogeneous, ranging from well-prognostic, transient skin erythema to the most devastating and often irreversible autoimmune-mediated congenital heart block (20).

4.1 The core pathogenic role of anti-Ro52 antibodies

Within this cohort, the most striking immunological feature is the universal positivity of anti-Ro52 antibodies across all nine patients (100%), with the vast majority presenting at exceptionally high quantitative titers (values ranging between 2.04 and 3.95). In contrast, standard qualitative testing for anti-SSA/Ro and anti-SSB/La demonstrated slight variability.

Case 5 serves as a potent clinical warning, routine qualitative testing for anti-SSA/Ro antibodies yielded a negative result, yet the patient exhibited definitive positivity for anti-Ro52 antibodies (2.80) alongside anti-SSB/La. Her newborn subsequently developed classic facial cutaneous NLE. This observation aligns with the current immunological consensus that anti-Ro52 antibodies may play a role in fetal tissue injury, where higher quantitative titers are often associated with an increased likelihood and severity of CHB (21).

Our results are highly consistent with existing research, Salomonsson et al. showing that 95% of them had a positive anti-Ro52 antibody titer, and the frequency of Ro60 and La antibodies was 63% and 58%, respectively (22). Bouyon's study confirmed that the risk of fetal cardiac complications increases when the mother has anti-SS-A and anti-SS-B antibodies, especially when specific anti-Ro52 antibodies are detected. Meanwhile, the risk of neonatal lupus is lower in women with low antibody titers (23).

4.2 Mechanistic insights into Ro52 disruption and interferon signaling

Ro52, formally classified as tripartite-motif-containing protein 21(TRIM21), is an intracellular receptor and E3 ubiquitin ligase of the TRIM family (24, 25).

Maternal anti-Ro52 antibodies competitively block its ligase activity by binding the UBE2E1 site, causing IRF3/5/7 dysregulation, which triggers persistent type I interferon inflammation and upregulates Ro52 expression, forming a positive feedback loop of damage (26–28).

Anti-Ro52 antibodies, especially those targeting the p200 epitope, are more strongly associated with congenital atrioventricular block than anti-Ro60 or anti-SSB antibodies (21). After transplacental transfer, they cross-react with fetal cardiomyocyte calcium channels, causing calcium dyshomeostasis, overload, and apoptosis (29, 30). Instead of silent clearance, maternal antibodies drive macrophage-mediated inflammatory phagocytosis, releasing abundant TNF-α and TGF-β, leading to atrioventricular node fibrosis, calcification, and permanent third-degree block (29, 31).

In this cohort, recurrent CHB (Case 1) and new-onset AVB (Case 9) were both linked to high anti-Ro52 antibody levels.

The three cardiac cases illustrate CHB's polarized prognosis. Although the baseline CHB risk in anti-Ro-positive primiparous women without prior adverse history is only 1%–2%, a previous infant with CHB or cutaneous NLE raises the recurrence risk to 17%–25%, with increased likelihood of cardiomyopathy and heart failure (32, 33).

4.3 Inspiration from HCQ and hormones for NLE

Eight mothers in our 9-case cohort were treated with HCQ during gestation. Biological models suggest that HCQ disrupts TLR-7/9 endosomal activation and downregulates pro-fibrotic signaling in macrophages (34, 35). Previous studies have associated maternal HCQ use with decreased CHB recurrence and favorable obstetric outcomes, consistent with the predominantly mild cutaneous or transient presentations observed in our infants. In this cohort, newborns of patients who took HCQ long-term mostly showed only mild skin lesions, and some intrauterine arrhythmias were reversed (36, 37).

The successful reversal of second-degree atrioventricular block in case 9 is the most important finding of this cohort. Third-degree CHB is usually irreversible due to fibrosis, while low-degree conduction block is in an active inflammatory stage and can respond to fluorinated glucocorticoids. Dexamethasone (4 mg/day) successfully suppressed fetal myocardial inflammation and prevented its progression to irreversible CHB. These observations call for routine fetal echocardiographic surveillance every 1–2 weeks between 16 and 26 weeks of gestation for high-risk pregnancies.

4.4 Multiple anticoagulation and anti-inflammatory strategies for mothers with NLE complicated by APS

Both patients had SLE complicated by APS. In addition to being positive for anti-SSA/SSB, their aCL IgG and β2GP1 were significantly elevated, indicating an extremely high risk of placental microthrombosis and a high risk of intrauterine fetal death or severe preeclampsia. Both patients received triple therapy with aspirin (100 mg/day), low molecular weight heparin (0.4 mL/day), and hydroxychloroquine, and both delivered successfully. Approximately 50% of mothers of infants with NLE are completely asymptomatic at delivery (38), and their high-titer antibodies are only discovered after neonatal diagnosis. However, long-term follow-up shows that more than half of asymptomatic mothers gradually develop autoimmune diseases several to more than ten years postpartum, most commonly SS, followed by SLE (39, 40).

In this cohort, the diagnosis time of SS in several mothers highly coincided with their pregnancy events, suggesting that NLE may be an early warning sign of occult maternal autoimmune diseases. Therefore, the experience of giving birth to a child with NLE should be regarded as a long-term warning of maternal health and requires continuous follow-up.

5 Conclusion

Maternal anti-Ro52 autoantibodies, particularly targeting the p200 epitope, are associated with an increased risk of NLE and multi-system organ involvement, especially fetal myocardial injury. While HCQ remains a key therapeutic option in high risk pregnancies, carefully timed immunomodulatory strategies warrant further exploration to evaluate their potential in mitigating conduction abnormalities before irreversible fibrosis develops. Given the small sample size, future prospective, multi-center studies are needed.

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Footnotes

Edited by: Abdulsamet Erden, Gazi University, Türkiye

Reviewed by: Özlem Karakaş, Ankara City Hospital, Türkiye

Busra Koksoy, Gazi University, Türkiye

Statements

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This study was supported by Sanming Project of Medicine in Shenzhen (SZSM202411006) and Shenzhen Second People's Hospital Clinical Research Fund of Shenzhen High-level Hospital Construction Project (2023yjlcyj024).

Data availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics approval

The studies involving humans were approved by Ethics Committee of Shenzhen Second People's Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

SC: Writing – review & editing, Writing – original draft. YJ: Writing – original draft. SZ: Writing – original draft. JH: Writing – original draft. XW: Writing – review & editing. HX: Writing – review & editing. MW: Writing – original draft, Writing – review & editing.

References

  1. 1. Vanoni F, Lava SAG, Fossali EF, Cavalli R, Simonetti GD, Bianchetti MG. Neonatal systemic lupus erythematosus syndrome: a comprehensive review. Clin Rev Allergy Immunol. (2017) 53 (3): 469 – 76. doi:10.1007/s12016-017-8653-0
  2. 2. Izmirly PM, Halushka MK, Rosenberg AZ, Whelton S, Rais-Bahrami K, Nath DS. Clinical and pathologic implications of extending the spectrum of maternal autoantibodies reactive with ribonucleoproteins associated with cutaneous and now cardiac neonatal lupus from SSA/Ro and SSB/La to U1RNP. Autoimmun Rev. (2017) 16 (9): 980 – 3. doi:10.1016/j.autrev.2017.07.013
  3. 3. Brucato A, Frassi M, Franceschini F, Cimaz R, Faden D, Pisoni MP. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum. (2001) 44 (8): 1832 – 5. 10.1002/1529-0131(200108)44:8<1832::AID-ART320>3.0.CO;2-C
  4. 4. Buyon JP, Clancy RM, Friedman DM. Cardiac manifestations of neonatal lupus erythematosus: guidelines to management, integrating clues from the bench and bedside. Nat Clin Pract Rheumatol. (2009) 5 (3): 139 – 48. doi:10.1038/ncprheum1018
  5. 5. Morel N, Lévesque K, Maltret A, Baron G, Hamidou M, Orquevaux P. Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus. Int J Cardiol. (2017) 248: 263 – 9. doi:10.1016/j.ijcard.2017.07.100
  6. 6. Llanos C, Izmirly PM, Katholi M, Clancy RM, Friedman DM, Kim MY. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum. (2009) 60 (10): 3091 – 7. doi:10.1002/art.24768
  7. 7. Li YQ, Wang Q, Luo Y, Zhao Y. Neonatal lupus erythematosus: a review of 123 cases in China. Int J Rheum Dis. (2015) 18 (7): 761 – 7. doi:10.1111/1756-185X.12652
  8. 8. Miyagawa S. Neonatal lupus erythematosus: a review of the racial differences and similarities in clinical, serological and immunogenetic features of Japanese versus Caucasian patients. J Dermatol. (2005) 32 (7): 514 – 22. doi:10.1111/j.1346-8138.2005.tb00793.x
  9. 9. Baltaci M, Fritsch P. Histologic features of cutaneous lupus erythematosus. Autoimmun Rev. (2009) 8 (6): 467 – 73. doi:10.1016/j.autrev.2008.12.014
  10. 10. Watson RM, Lane AT, Barnett NK, Bias WB, Arnett FC, Provost TT. Neonatal lupus erythematosus. A clinical, serological and immunogenetic study with review of the literature. Medicine (Baltimore). (1984) 63 (6): 362 – 78. doi:10.1097/00005792-198411000-00003
  11. 11. Neiman AR, Lee LA, Weston WL, Buyon JP. Cutaneous manifestations of neonatal lupus without heart block: characteristics of mothers and children enrolled in a national registry. J Pediatr. (2000) 137 (5): 674 – 80. doi:10.1067/mpd.2000.109108
  12. 12. Provost TT, Watson R, Gammon WR, Radowsky M, Harley JB, Reichlin M. The neonatal lupus syndrome associated with U1RNP (nRNP) antibodies. N Engl J Med. (1987) 316 (18): 1135 – 8. doi:10.1056/NEJM198704303161807
  13. 13. Sun W, Fu C, Jin X, Lei C, Zhu X. Neonatal lupus erythematosus: an acquired autoimmune disease to be taken seriously. Ann Med. (2025) 57 (1): 2476049. doi:10.1080/07853890.2025.2476049
  14. 14. Derdulska JM, Rudnicka L, Szykut-Badaczewska A, Mehrholz D, Nowicki RJ, Barańska-Rybak W. Neonatal lupus erythematosus—practical guidelines. J Perinat Med. (2021) 49 (5): 529 – 38. doi:10.1515/jpm-2020-0543
  15. 15. Brucato A, Cimaz R, Caporali R, Ramoni V, Buyon J. Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. Clin Rev Allergy Immunol. (2011) 40 (1): 27 – 41. doi:10.1007/s12016-009-8190-6
  16. 16. Erden A, Fanouriakis A, Kiliç L, Sari A, Armağan B, Bilgin E. Geoepidemiology and clinical characteristics of neonatal lupus erythematosus: a systematic literature review of individual patients’ data. Turk J Med Sci. (2020) 50 (1): 281 – 90. doi:10.3906/sag-1910-39
  17. 17. Vadasz B, Chen P, Yougbaré I, Zdravic D, Li J, Li C. Platelets and platelet alloantigens: lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia. Genes Dis. (2015) 2 (2): 173 – 85. doi:10.1016/j.gendis.2015.02.003
  18. 18. Holt PG, Jones CA. The development of the immune system during pregnancy and early life. Allergy. (2000) 55 (8): 688 – 97. doi:10.1034/j.1398-9995.2000.00118.x
  19. 19. Ygberg S, Nilsson A. The developing immune system—from foetus to toddler. Acta Paediatr. (2012) 101 (2): 120 – 7. doi:10.1111/j.1651-2227.2011.02494.x
  20. 20. Jin X, Sun W, Li Y, Liu X, Sun Z, Wang H. Clinical characteristics of neonatal lupus erythematosus complicated by congenital heart block: a multi-center retrospective study in east China. Sci Rep. (2025) 15 (1): 14031. doi:10.1038/s41598-025-98368-3
  21. 21. Strandberg L, Winqvist O, Sonesson SE, Mohseni S, Salomonsson S, Bremme K. Antibodies to amino acid 200-239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block. Clin Exp Immunol. (2008) 154 (1): 30 – 7. doi:10.1111/j.1365-2249.2008.03732.x
  22. 22. Salomonsson S, Dzikaite V, Zeffer E, Eliasson H, Ambrosi A, Bergman G. A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block. Scand J Immunol. (2011) 74 (5): 511 – 7. doi:10.1111/j.1365-3083.2011.02610.x
  23. 23. Buyon JP, Winchester RJ, Slade SG, Arnett F, Copel J, Friedman D. Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. Comparison of enzyme-linked immunosorbent assay and immunoblot for measurement of anti-SS-A/Ro and anti-SS-B/La antibodies. Arthritis Rheum. (1993) 36 (9): 1263 – 73. doi:10.1002/art.1780360911
  24. 24. Oke V, Wahren-Herlenius M. The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review. J Autoimmun. (2012) 39 (1–2): 77 – 82. doi:10.1016/j.jaut.2012.01.014
  25. 25. Zhang Z, Bao M, Lu N, Weng L, Yuan B, Liu YJ. The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA. Nat Immunol. (2013) 14 (2): 172 – 8. doi:10.1038/ni.2492
  26. 26. Liu Y, Xu M, Min X, Wu K, Zhang T, Li K. TWEAK/Fn14 activation participates in Ro52-mediated photosensitization in cutaneous lupus erythematosus. Front Immunol. (2017) 8: 651. doi:10.3389/fimmu.2017.00651
  27. 27. Espinosa A, Dardalhon V, Brauner S, Ambrosi A, Higgs R, Quintana FJ. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med. (2009) 206 (8): 1661 – 71. doi:10.1084/jem.20090585
  28. 28. Jones EL, Laidlaw SM, Dustin LB. TRIM21/Ro52—roles in innate immunity and autoimmune disease. Front Immunol. (2021) 12: 738473. doi:10.3389/fimmu.2021.738473
  29. 29. Eftekhari P, Sallé L, Lezoualc'h F, Mialet J, Gastineau M, Briand JP. Anti-SSA/Ro52 autoantibodies blocking the cardiac 5-HT4 serotoninergic receptor could explain neonatal lupus congenital heart block. Eur J Immunol. (2000) 30 (10): 2782 – 90. 10.1002/1521-4141(200010)30:10<2782::AID-IMMU2782>3.0.CO;2-9
  30. 30. Xiao GQ, Hu K, Boutjdir M. Direct inhibition of expressed cardiac l- and t-type calcium channels by igg from mothers whose children have congenital heart block. Circulation. (2001) 103 (11): 1599 – 604. doi:10.1161/01.CIR.103.11.1599
  31. 31. Clancy RM, Askanase AD, Kapur RP, Chiopelas E, Azar N, Miranda-Carus ME. Transdifferentiation of cardiac fibroblasts, a fetal factor in anti-SSA/ro-SSB/la antibody-mediated congenital heart block. J Immunol. (2002) 169 (4): 2156 – 63. doi:10.4049/jimmunol.169.4.2156
  32. 32. Man R, Le Vance J, Abdullahi H, Davenport C, Yuan M, Ormesher L. Maternal and fetal outcomes in subsequent pregnancies after peripartum cardiomyopathy: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. (2025) 104 (6): 1009 – 25. doi:10.1111/aogs.15117
  33. 33. Wijayanto MA, Myrtha R, Lukas GA, Rahma AA, Hanifa SN, Zahira HA. Outcomes of subsequent pregnancy in women with peripartum cardiomyopathy: a systematic review and meta-analysis. Open Heart. (2024) 11 (1): e002626. doi:10.1136/openhrt-2024-002626
  34. 34. Zheng H, Zhang Y, He J, Yang Z, Zhang R, Li L. Hydroxychloroquine inhibits macrophage activation and attenuates renal fibrosis after ischemia-reperfusion injury. Front Immunol. (2021) 12: 645100. doi:10.3389/fimmu.2021.645100
  35. 35. Zhang SH. Role of hydroxychloroquine in prevention of congenital heart block in pregnant women with positive anti-Ro/SSA and/or anti-La/SSB. Aust N Z J Obstet Gynaecol. (2026) 66 (2): e70105. doi:10.1111/ajo.70105
  36. 36. Saleh ZF, Somers EC, Romero VC, Marder W. Hydroxychloroquine in systemic lupus erythematosus, anti-SSA/SSB, and antiphospholipid antibody-positive pregnancies. Am J Obstet Gynecol. (2026) 234 (1): 7 – 20. doi:10.1016/j.ajog.2025.09.002
  37. 37. Izmirly P, Kim M, Friedman DM, Costedoat-Chalumeau N, Clancy R, Copel JA. Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/ro-positive mothers. J Am Coll Cardiol. (2020) 76 (3): 292 – 302. doi:10.1016/j.jacc.2020.05.045
  38. 38. Zdraveska N, Kostovski A, Sofijanova A, Jancevska S, Jovanovska J, Kacarska M. Neonatal lupus erythematosus-a rare syndrome of transient autoimmunity. Clin Case Rep. (2022) 10 (6): e6004. doi:10.1002/ccr3.6004
  39. 39. Diaz T, Danguecan A, Dominguez D, Knight A, Laskin CA, Levy DM. Long-term outcomes of children born to anti-Ro antibody-positive mothers with and without rheumatic disease. Arthritis Care Res (Hoboken). (2025) 77 (7): 848 – 54. doi:10.1002/acr.25510
  40. 40. Ma J, Quan M, Gao J, Song Y, Li Z, Song H. Long-term follow-up of offspring of mothers with systemic lupus erythematosus: an observational study. Clin Rheumatol. (2026) 45 (2): 1291 – 8. doi:10.1007/s10067-025-07893-z

Citation

Cheng, S., et al. (2026). The pathogenic role of high-titer anti-Ro52 antibodies in neonatal lupus erythematosus: insights from a 9 case series. Frontiers in Pediatrics, Volume 14. https://doi.org/
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14 - 2026

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© 2026 Cheng, Jiang, Zhang, Huang, Wang, Xie and Wang.

License: https://creativecommons.org/licenses/by/4.0/

*Correspondence: Meiying Wang

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