Patients with lupus have “dramatically” low serum levels of the biologically active form of vitamin D, which may contribute to the pathological processes involved in their disease, Dr. Peter E. Lipsky said recently at a rheumatology meeting sponsored by New York University.
Previous research has shown that 1,25(OH)2D3 is an important regulator of lymphocyte and dendritic cell function, and many patients who have autoimmune diseases such as lupus are known to be deficient in this vitamin.
To test the hypothesis that vitamin D deficiency is contributing to the lymphocyte overactivity characteristic of lupus, investigators measured the serum levels of 1,25(OH)2D3 as well as 25(OH)D in 57 patients with lupus. The researchers then compared those patients' levels with the levels of 29 patients with rheumatoid arthritis and 28 healthy controls, according to Dr. Lipsky, chief of the Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The mean age of the lupus patients was 34 years and their mean disease duration was 5 years. In all, 90% were female, and the patients' mean SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score was 6.5.
Patients who had lupus also had very low levels of 25(OH)D (mean 11.5 ng/mL), compared with the patients in the healthy (mean 59.2 ng/mL) and RA (mean 54.6 ng/mL) groups.
The serum levels of 25(OH)D were equally low among patients with newly diagnosed disease (11.6 ng/mL), compared with those having longstanding disease (11.8 ng/mL).
Detailed analysis of these serum samples found lower 1,25(OH)2D3 levels correlated with disease activity. Levels were significantly lower among patients whose SLEDAI scores were greater than 4 (mean 12.2 pg/mL) than among those with scores at or below 4 (mean 19.4 pg/mL).
The levels also were significantly lower in patients who were antinuclear antibody positive (14.4 pg/mL), compared with those patients who were antibody negative (22 pg/mL) (J. Immunol. 2007;179:1634–47).
A pronounced feature of lupus is the presence of multiple B-cell abnormalities, including a massive expansion of memory cells and transitional cells from the bone marrow, along with a tremendous increase in plasma cells, Dr. Lipsky explained.
Further analysis of the serum samples of the lupus patients revealed that 1,25(OH)2D3 interferes with B-cell function and response, by inhibiting the normal events of proliferation, plasma cell differentiation, immunoglobulin production, and the generation of memory cells.
The mechanism of inhibition by vitamin D appears to relate to induction of the cell cycle regulator p27, he said.
“The result of this is B lymphocyte overactivity, because activated B cells express many of the molecules involved in vitamin D metabolism. This leads to a vicious cycle” in which B cells are overactive and they metabolize vitamin D, said Dr. Lipsky.
The B cells then become more vitamin D deficient, and become more overactive, he added.
“Those who have tried to replenish vitamin D levels in [patients with lupus] know that it takes a very large amount to bring them up to normal levels,” he said.
Nonetheless, the results of this study indicate that further trials of complete vitamin D replenishment in lupus are warranted, Dr. Lipsky concluded.
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