Introduction The effects of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) on CMV infection in patients with autoimmune diseases receiving immunosuppressants have not been explored. Methods Patients with active systemic lupus erythematosus (SLE) were preemptively monitored for clinically significant CMV infection (CsCMVI, defined as plasma CMV DNA loads > 3 log10 IU/mL). CMV-specific CMI was assessed using an enzyme-linked immunosorbent assay (QuantiFERON-CMV®, QF) before as well as 1 and 3 months after intense immunosuppressive therapy. Results The study included 55 patients with active SLE; patients had a mean age of 34 years (standard deviation [SD] 13 years), a median SLEDAI-2K score of 14 (SD 8), and 93% were female. Most patients had renal involvement (67%), received methylprednisolone (93%), and were CMV seropositive (95%). Thirteen (23.6%) patients developed CsCMVI. Among patients with active SLE who were QF-negative (QF–) and QF-positive (QF+) before receiving immunosuppressive therapy, 28.6% and 25% developed CsCMVI, respectively (p=0.69). However, 1 month post-immunosuppression, more QF– than QF+ patients developed CsCMVI (44.4% vs. 11.8%, p=0.03; adjusted hazard ratio 4.97 [95% confidence interval 1.07–23.10], p=0.04). Conclusions Patients with active SLE and low CMV-specific T cell responses could develop CMV infection after receiving immunosuppressants. Further studies should focus on CMV-specific CMI among patients with autoimmune diseases.

BackgroundBy depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines’ humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear.ObjectiveTo estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients.MethodsThis retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were <25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2.FindingsForty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients.ConclusionsNine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.

Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-tocreatinine ratio of ‡ 30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46-57) years, 86% male, median (IQR) CD4 count of 489 (341-638) cells/ mm 3 , 85% with HIV RNA < 50 copies/ml], 18 subjects (16.2%) had moderately increased albuminuria (albuminuria range between 30 and 300 mg/g) and 2 subjects (1.8%) had severely increased albuminuria (albuminuria more than 300 mg/g). In multivariable logistic models, sE-selectin, sVCAM-1, CRP, SAA, and SAP remained significantly associated with albuminuria after adjustment of CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIVinfected patients.