evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people around the world 1 . Brazil is among those countries with the highest numbers of confirmed cases of, and deaths from, SARS-CoV-2 (refs. 1,2 ), with >430,000 deaths registered and approximately 15 million cases as of May 2021 (ref. 1 ). A second infection wave was driven by the Gamma coronavirus variant 3 , which is considered to be 2.5-fold more contagious than the original strain 4 and possibly associated with a higher risk for hospitalization and intensive care unit admission in patients younger than 60 years of age 5 . This second peak in March and April 2021 resulted in more than double the reported coronavirus disease 2019 (COVID-19) cases of the first peak in 2020 (ref. 6 ). Vaccines are therefore essential in regard to reducing COVID-19 mortality and morbidity.Although phase 3 clinical trials results are still being consolidated in China,
Objective
To assess circulating follicular helper-like CD4+ T (cTfh-like) cells in systemic lupus erythematosus (SLE) and determine their relationship to disease activity.
Methods
We analyzed blood samples from SLE patients, and as controls, Behçet’s disease (BD) patients and healthy individuals. We used flow cytometry to enumerate cTfh-like cells using as markers the C-X-C chemokine receptor type 5 (CXCR5), inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PCDC1, PD-1), and secretion of interleukin-21 (IL-21). We compared the frequency of cTfh-like cells with that of circulating plasmablasts (CD19+IgD−CD38+) and evaluated their possible association with disease activity.
Results
cTfh-like T cells, identified as CXCR5hiICOShiPD-1hi, were expanded in the blood of SLE patients compared to BD and healthy controls. Such cells produced IL-21 with lower expression of CCR7, compared to circulating CXCR5hi central memory (Tcm) cells, enabling their distinction. PD-1, not ICOS or CXCR5, expression was significantly elevated in cTfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5hi cTfh-like cells correlated with disease activity, circulating plasmablasts, and anti-dsDNA antibody positivity, but not disease duration nor past organ injury; rather, it reflected current active disease.
Conclusion
We found that cTfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T-B cell collaboration with a causal relationship central to disease pathogenesis. These findings also suggest that cTfh-like cells provide a surrogate for aberrant GC activity in SLE, and that their PD-1 expression offers a tool for following disease activity and response to therapies.
The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644).
We have evaluated 36 consecutive systemic lupus erythematosus (SLE) female patients, age 18-39 years, without current or previous alkylating therapy, in order to determine the prevalence of the menstrual disturbances and their clinical, hormonal and therapeutic associations. Seventeen patients presented normal cycles, whereas menstrual alterations were observed in 19. Ovarian function was generally preserved in these groups. Sub-clinical thyroid disease (normal free T4 and elevated TSH) and slightly increased prolactin levels were detected in 8% of patients, with comparable frequencies in both groups. Similarly, the current use of azathioprine was not associated with menstrual disturbances. Percentages of prednisone current use (P = 0.3), mean dose (P = 0.062), and percentages of patients on high doses (> or = 30 mg/day; P = 0.09) were comparable in patients with or without menstrual alterations. In contrast, the mean SLEDAI levels (P = 0.02) and the frequency of patients with SLEDAI > or = 8 (P = 0.008) were higher in patients with irregular cycles. Interestingly, 5/7 (71%) of the patients with menstrual disturbances and a new significant flare (SLEDAI > or = 8) were evaluated before the introduction of high dose steroid, supporting the idea that disease activity is a major factor in menstrual disorders in SLE patients without alkylating therapy.
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