Abstract
Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (TFH) and T follicular regulatory cells (TFR), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with fewer TFH and increased TFR. Together, the data support use of Prevnar vaccination in individuals with SLE.
Highlights
Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease with complex genetic and immune system pathogenic mechanisms operative throughout the disease course [1, 2]
Our data indicate that anti-pneumococcal vaccine Prevnar13, effectively produces humoral polysaccharide capsule (PPS)-specific immunity in lupus-prone MRL-lpr mice, while ameliorating disease severity, a phenomenon associated with reduced T follicular helper cells (TFH) cells
SLE patients are at increased risk for Streptococcus pneumoniae infection [9, 11], vaccination coverage remains dramatically low [32]
Summary
Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease with complex genetic and immune system pathogenic mechanisms operative throughout the disease course [1, 2]. A high percentage of anti-bacterial antibodies against Streptococcus pneumoniae produced in patients with lupus are capable of binding double-stranded DNA [23]. These findings are cause for concern despite official recommendations. Despite justified concerns preventing guideline enaction, mechanistic studies investigating the effect of Prevnar-13 on immune function in SLE are lacking. To address this issue, we report effects of Prevnar-13 on immunological and clinical parameters of the lupus-like disease occurring in MRL-lpr mice
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