Objective To evaluate seroreactivity and disease flares after COVID‐19 vaccination in a multi‐ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). Methods 90 SLE patients and 20 healthy controls receiving a complete COVID‐19 vaccine regimen were included. IgG seroreactivity to the SARS‐CoV‐2 spike receptor‐binding domain (RBD) and SARS‐CoV‐2 microneutralization were used to evaluate B cell responses; IFN‐γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. Results Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS‐CoV‐2 spike RBD than controls. Twenty‐six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti‐dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS‐CoV‐2 Spike RBD strongly correlated with the SARS‐CoV‐2 microneutralization titers and antigen‐specific IFN‐γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN‐γ production was likewise diminished. Pre‐/post‐vaccination SLEDAI scores were similar. Only 11.4% of patients had a post‐vaccination flare; 1.3% were severe. Conclusion In a multi‐ethnic/racial study of SLE patients 29% had a low response to the COVID‐19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.

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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.

Gout is a common rheumatic condition, with increasing prevalence in recent decades. The mainstay of treatment for gout is oral urate-lowering therapy (ULT), typically with xanthine oxidase inhibitors (XOIs). Unfortunately, a proportion of patients have persistent gout that is refractory to ULT. Pegloticase, a recombinant pegylated uricase, has been approved by the US Food and Drug Administration for the treatment of refractory gout. However, concern has been raised regarding the risk of infusion reactions, which are now understood to be largely due to the development of antipegloticase antibodies. Discontinuation of pegloticase upon failure to lower serum urate has been shown to markedly reduce infusion reaction risk, but deprives patients of what, in many cases, is a last-resort treatment. In this manuscript, we review the rationale, mechanism of action, efficacy and safety of pegloticase. Additionally, we focus on potential strategies to reduce pegloticase immunogenicity and potentially make this important agent available to a wider group of patients requiring treatment.

Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vs 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset.Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2.

Accurately quantifying parent estrogens (PE) estrone (E1) and estradiol (E2) and their metabolites (EM) within breast tissue and serum may permit detailed investigations of their contributions to breast carcinogenesis among BRCA1/2 mutation carriers. We conducted a study of PE/EM in serum, nipple aspirate fluid (NAF), and ductal lavage supernatant (DLS) among postmenopausal BRCA1/2 mutation carriers. PE/EM (conjugated and unconjugated) were measured in paired serum/NAF (n = 22 women) and paired serum/DLS samples (n = 24 women) using quantitative liquid chromatography–tandem mass spectrometry (LC/MS/MS). The relationships between serum and tissue-specific PE/EM were measured using Pearson’s correlation coefficients. Conjugated forms of PE/EM constituted the majority of estrogen in serum (88 %), NAF (59 %) and DLS (69 %). PE/EM in NAF and serum were highly correlated [E1 (r = 0.97, p < 0.0001), E2 (r = 0.90, p < 0.0001) and estriol (E3) (r = 0.74, p < 0.0001)] as they were in DLS and serum [E1 (r = 0.92, p < 0.0001; E2 (r = 0.70, p = 0.0001; E3 (r = 0.67, p = 0.0004)]. Analyses of paired total estrogen values for NAF and serum, and DLS and serum yielded ratios of 0.22 (95 % CI 0.19–0.25) and 0.28 (95 % CI 0.24–0.32), respectively. This report is the first to employ LC/MS/MS to quantify PE/EM in novel breast tissue-derived biospecimens (i.e., NAF and DLS). We demonstrate that circulating PE and EM are strongly and positively correlated with tissue-specific PE and EM measured in NAF and DLS among post-menopausal BRCA1/2 mutation carriers. If confirmed, future etiologic studies could utilize the more readily obtainable serum hormone levels as a reliable surrogate measure of exposure at the tissue level.

Objective Using the Manhattan Lupus Surveillance Program, a multiracial/ethnic population‐based registry, we aimed to compare 3 commonly used classification criteria for systemic lupus erythematosus (SLE) to identify unique cases and determine the incidence and prevalence of SLE using the EULAR/American College of Rheumatology (ACR) criteria. Methods SLE cases were defined as fulfilling the 1997 ACR, the Systemic Lupus International Collaborating Clinics (SLICC), or the EULAR/ACR classification criteria. We quantified the number of cases uniquely associated with each and the number fulfilling all 3 criteria. Prevalence and incidence using the EULAR/ACR classification criteria and associated 95% confidence intervals (95% CIs) were calculated. Results A total of 1,497 cases fulfilled at least 1 of the 3 classification criteria, with 1,008 (67.3%) meeting all 3 classifications, 138 (9.2%) fulfilling only the SLICC criteria, 35 (2.3%) fulfilling only the 1997 ACR criteria, and 34 (2.3%) uniquely fulfilling the EULAR/ACR criteria. Patients solely satisfying the EULAR/ACR criteria had <4 manifestations. The majority classified only by the 1997 ACR criteria did not meet any of the defined immunologic criteria. Patients fulfilling only the SLICC criteria did so based on the presence of features unique to this system. Using the EULAR/ACR classification criteria, age‐adjusted overall prevalence and incidence rates of SLE in Manhattan were 59.6 (95% CI 55.9–63.4) and 4.9 (95% CI 4.3–5.5) per 100,000 population, with age‐adjusted prevalence and incidence rates highest among non‐Hispanic Black female patients. Conclusion Applying the 3 commonly used classification criteria to a population‐based registry identified patients with SLE fulfilling only 1 validated definition. The most recently developed EULAR/ACR classification criteria revealed prevalence and incidence estimates similar to those previously established for the ACR and SLICC classification schemes.

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