Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.

Phenotypic and Functional Consequences of PLT Binding to Monocytes and Its Association with Clinical Features in SLE

“…The lowest percentages of CD14+PLT+ were found in SLE patients with active disease and renal manifestations. This seems to contradict our previous studies, which showed that SLE patients with active disease and renal manifestations had the highest percentages of B and T lymphocytes with bound PLTs [ 62 ]. However, we found no correlation between the percentages of myeloid and lymphoid cells with bound PLTs ( Figure S5 ) in these patients.…”

“…IL-10 or TNF-α production was analyzed on CD14 +PLT-, CD14 +PLT+CD62P-, and CD14+PLT+CD62P+ monocytes after ultrapure TLR4 agonist lipopolysaccharide (LPS) (Invivogen, San Diego, CA, USA) stimulation using the IL-10 or TNF-α secretion assay (MiltenyiBiotec), as previously described [ 62 ]. Briefly, after 4 hours of LPS stimulation (1 µg/mL), PBMCs were labeled with IL-10- or TNF-α-specific catch reagent and incubated under slow rotation.…”

The role of platelets in immune-mediated inflammatory diseases

“… 15 ). However, a descriptive study in humans found that levels of platelet–B cell aggregates were increased in patients with SLE and correlated with circulating levels of preswitched memory B cells and immunoglobulins 142 . Mechanistically, in vitro data suggest that co-culture of human B cells with platelets leads to increased immunoglobulin production and antibody class-switching, most likely through the CD40L–CD40 axis 143 .…”

The Dual Role of Platelets in the Cardiovascular Risk of Chronic Inflammation

“…High levels of lymphocytes-PLTs aggregates were observed in SLE and psoriasis. In SLE, lymphocytes-PLTs aggregates had an up-regulation of CD86, B cell activation factor receptor and IL-10 production and correlated positively with plasmatic levels of IgG, IgA, IL-10, sCD40L and renal manifestation, and correlated negatively with IgM levels ( 100 ). In psoriasis, the IL-17+ CD4+ had higher levels of bound PLTs and anti-TNF-α drugs normalize the numbers ( 101 ), while in HIV there are more lymphocytes-PLTs aggregates and are associated to D-dimer levels, increasing the CV risk ( 116 ).…”