Cell activation, PD-1 expression and in vitro cytokine production in patients with juvenile systemic lupus erythematosus.

BACKGROUND: Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease. OBJECTIVE: To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls. METHODOLOGY: Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin. RESULTS: jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls (p = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls (p = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (p=0.080) and higher concentrations of IL-23 (p = 0.063) than controls. CONCLUSIONS: jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.

Adequate tetanus but poor diphtheria and pertussis response to a Tdap booster in adolescents with juvenile systemic lupus erythematosus.

BACKGROUND: Reports on vaccine responses in immunocompromised patients, such as juvenile systemic lupus erythematosus (jSLE), have shown highly variable results. OBJECTIVE: To compare the immune response and safety after a Tdap booster in 26 jSLE patients and 26 matched healthy adolescents.Methodology: Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole cell pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Both groups showed a similar frequency of adverse events. There was no evidence of disease reactivation after Tdap booster in the jSLE cohort. Both groups showed a significant increase in antibody titers for all three antigens on D14 and D28 (p < 0.001). jSLE patients had a significantly lower increase in diphtheria titers than the control group (p = 0.007). jSLE patients had a distinct titer increase of tetanus and pertussis antibodies when compared to controls (p = 0.004 and p < 0.001, respectively). There was a lower frequency of pertussis seroconversion in the jSLE group on D14 (p = 0.009), D28 (p = 0.023), D12m (p = 0.015) and D24m (p = 0.004). Cellular immune response to Bordetella pertussis showed significantly lower levels of IFNγ (p < 0.001) and higher levels of IL10, IL12, IL21 and TNFα in jSLE patients than controls. CONCLUSIONS: jSLE patients had good response to Tdap booster dose for the tetanus antigen, but not for diphtheria and pertussis. This vaccine was safe in relation to adverse events and absence of disease reactivation.