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Objective Neonatal lupus (NL) occurs in fetuses exposed to maternal anti-SSA/Ro and/or anti-SSB/La antibodies, although the mothers themselves may not manifest any clinical disease. A focus on transmission of risk factors for NL from maternal grandparents to mothers of children with NL may yield dividends toward understanding the aggregation of autoantibodies and genetic factors in affected families. This study was perforned to determine the role of maternal grandparents in the development of the autoimmune phenotype of mothers of children with NL. Methods Fifty-one mothers of children with cardiac and/or cutaneous NL, 48 maternal grandmothers, and 35 maternal grandfathers in the Research Registry for Neonatal Lupus were interrogated for clinical symptoms by questionnaire and underwent laboratory assessments, including determination of anti-SSA/Ro and anti-SSB/La antibody status (by enzyme-linked immunosorbent assay) and genotype at rs1800629 ( TNFα) and rs7775397 ( C6orf10) (allelic discrimination). The transmission disequilibrium test (TDT) was computed to test for nonrandom transmission from maternal grandparents to mothers of children with NL. Results The common phenotypic feature in mothers of children with NL was the autoantibody and not the clinical profile; 7 had lupus, 14 had Sjögren's syndrome, 7 had both, and 23 were asymptomatic. Mothers of children with NL were significantly enriched for the risk alleles at both TNFα and C6orf10. The grandparents of children with NL carried minimal burden for autoimmune disease or abnormal antibody production and were not enriched in the genetic risk factors. However, the TDT analysis showed significant excess transmission of the risk alleles at both TNFα (odds ratio [OR] 6.67, P = 3.93 × 10−4) and C6orf10 (OR 35.0, P = 3.74 × 10−5) to mothers of children with NL. Conclusion Mothers of children with NL are enriched for the TNFα and C6orf10 risk alleles, which are preferentially inherited from the asymptomatic maternal grandparents. These findings support the hypothesis that the development of NL and genetic etiology are multigenerational. [ABSTRACT FROM AUTHOR]

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self‐identified Black race. Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.gov identifier: NCT01632241) was a 52‐week multicenter, double‐blind, placebo‐controlled trial in adults of self‐identified Black race with active SLE who received monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26‐week open‐label extension phase included patients who completed the double‐blind phase. The primary end point of the study was SLE Responder Index (SRI) response rate at week 52 with modified proteinuria scoring adapted from the SLE Disease Activity Index 2000 (SLEDAI‐2K) (SRI–SLEDAI‐2K). Key secondary end points included SRI response rate at week 52, time to first severe SLE flare, and reductions in prednisone dose. Results: The modified intent‐to‐treat population comprised 448 patients, of whom 96.9% were women and the mean ± SD age was 38.8 ± 11.42 years. The primary end point (improvement in the SRI–SLEDAI‐2K response rate at week 52) was not achieved (belimumab 48.7%, placebo 41.6%; odds ratio 1.40 [95% confidence interval 0.93, 2.11], P = 0.1068); however, numerical improvements favoring belimumab were observed, in which the SRI–SLEDAI‐2K response rates were higher in those who received belimumab compared with those who received placebo, especially in patients with SLE who had high disease activity or renal manifestations at baseline. The safety profile of belimumab was generally consistent with that observed in previous SLE trials. Adverse events were the primary reasons for double‐blind phase withdrawals (belimumab 5.4%, placebo 6.7%). Conclusion: The primary end point of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry. [ABSTRACT FROM AUTHOR]

Objective: To characterize patients with systemic lupus erythematosus (SLE) affected by coronavirus disease 2019 (COVID‐19) and to analyze associations of comorbidities and medications on infection outcomes. Methods: Patients with SLE and reverse transcriptase–polymerase chain reaction–confirmed COVID‐19 were identified through an established New York University lupus cohort, query of 2 hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web‐based questionnaire and review of medical records. Data on baseline characteristics were obtained for all patients with COVID‐19 to analyze risk factors for hospitalization. Data were also collected on asymptomatic patients and those with COVID‐19–like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID‐19–positive patients. Results: A total of 226 SLE patients were included: 41 with confirmed COVID‐19, 19 who tested negative for COVID‐19, 42 with COVID‐19–like symptoms who did not get tested, and 124 who remained asymptomatic without testing. Of the SLE patients with confirmed COVID‐19, hospitalization was required in 24 (59%) and intensive care unit–level of care in 4, and 4 died. Hospitalized patients tended to be older, nonwhite, Hispanic, have higher body mas index (BMI), history of nephritis, and at least 1 comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least 1 comorbidity, and BMI as independent predictors of hospitalization. Conclusion: In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID‐19 outcomes in patients with SLE. [ABSTRACT FROM AUTHOR]