Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Vitamin D Deficiency Is Associated with B Cell Hyperreactivity in Systemic Lupus Erythematosus
Cole1, Lauren R., Macwana2, Susan, Lu2, Rufei, Klein2, Wendy, Roberts2, Virginia, Dedeke1, Amy, Crowe2, Sherry R.
Autoimmune diseases have complex etiologies, likely including variable interactions between genetic predispositions and environmental risks. Vitamin D (Vit D) deficiency has recently been linked with many autoimmune disorders, including systemic lupus erythematosus (SLE). Vit D inhibits antibody secretion and autoantibody production in B cells of animal models; however, the influence of Vit D deficiency on autoantibody production and antigen specific immune responses in SLE patients is unknown. Our study tests whether Vit D deficiency is associated with SLE B cell hyperreactivity or improved antigen-specific antibody responses.
This study enrolled 92 SLE patients who met ACR criteria and matched controls. 25-hydroxyvitamin D (25D) levels, lupus-associated autoantibodies (Ro, La, Sm, nRNP, ribosomal P, dsDNA, ANAs and phospholipid antibodies) and influenza humoral immune response parameters including Bmax (relative amounts of anti-influenza antibodies against native or denatured antigen, measured separately), Ka (relative affinity), and hemagglutination inhibition (relative protective antibody response) were measured. Isolated PBMCs were used for multiparameter PhosFlow analysis of downstream B cell activation markers such as phospho-LYN (pY397 and pY508) and phospho-ERK1/2 (pERK1/2).
SLE patients and autoantibody-positive controls were significantly more likely to be Vit D deficient than autoantibody-negative controls, 75% vs 65% vs 25%, respectively (p=0.0003 and p=0.0124). Additionally, anti-Ro positive SLE patients had significantly lower 25D levels than anti-Ro negative SLE patients (p=0.0311). In SLE patients, we saw a significant negative correlation between 25D levels and their humoral immune response to influenza vaccination (p=0.004, r2=0.189). Furthermore, decreased vitamin D levels in SLE patients were correlated with hyperreactive B cells as measured by pY508LYN and pERK1/2. This correlation with 25D was seen in anti-IgM F(ab)'2 and PMA stimulated B cells ([PMA: pY508LYN p=0.002, pERK1/2 p=0.014][anti-IgM F(ab)'2: pY508LYN, p=0.018]), as well as in unstimulated B cells (pY508LYN p=0.019, pERK1/2 p=0.029).
Our evidence suggests a role for Vit D deficiency in human B cell hyperreactivity and autoantibody production. We saw an increase in Vit D deficiency in autoantibody-positive controls that is similar to what is seen in SLE patients. Supporting the idea that Vit D deficiency leads to increased B cell activity, we saw a negative correlation between Vit D levels and the ability to mount a humoral immune response to the flu vaccine. The increase in B cell activity was corroborated by flowcytometric data indicating increased phosphorylation of LYN and ERK1/2 in Vit D deficient patients.
To cite this abstract, please use the following information:
Cole, Lauren R., Macwana, Susan, Lu, Rufei, Klein, Wendy, Roberts, Virginia, Dedeke, Amy, et al; Vitamin D Deficiency Is Associated with B Cell Hyperreactivity in Systemic Lupus Erythematosus [abstract]. Arthritis Rheum 2009;60 Suppl 10 :580