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Lupus patients have extremely low levels of vitamin D.

NEW YORK -- Patients with lupus have "dramatically" low serum levels of the biologically active form of vitamin D, a deficiency that may contribute to the pathological processes involved in their disease, Dr. Peter E. Lipsky said at a rhematology meeting sponsored by New York University.

Previous work has shown that 1,25 (OH)[sub.2][D.sub.3] is an important regulator of lymphocyte and dendritic cell function, and many patients with autoimmune diseases are deficient in this vitamin.

To test the hypothesis that vitamin D deficiency is contributing to the lymphocyete overactivity characteristic of lupus, investigators measured serum levels of 1, 25 (OH)[sub.2][D.sub.3] and 25 (OH)D in 57 patients with lupus and compared their levels with those 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.

Mean age of the lupus patients was 34 years and mean disease duration was 5 years. In all, 90% were female, and their mean SLEDAL (Systemic Lupus Erythe-matosus Disease Activity Index) score was 6.5.

Patients with lupus had very low levels of 25(OH)D (mean 11.5 ng/mL), compared with those in the control (mean 59.2 ng/mL) and rhematoid arthritis (mean 54.6 ng/mL) groups.

The 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 that lower 1,25 [(OH).sub.2] ] [D.sub.3] levels correlated with disease activity, with levels being 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).

Levels also were significantly lower in patients who were antinuclear antibody positive (14.4 pg/mL), compared with those 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 l,25(OH)[sub.2]D[sub.3] 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 overacitivity, became 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. The B cells then become more vitamin D deficient, and become more overactive, Dr. Lipsky said.

"'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 a trial of complete vitamin D replenishment in lupus is warranted, he concluded.


New York Bureau
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Title Annotation:Rheumatology
Publication:Internal Medicine News
Geographic Code:1USA
Date:Jun 15, 2008
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