Reduced CD5(+) CD24(hi) CD38(hi) and interleukin-10(+) regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies.

Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (Bregs ), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+) CD24(hi) CD27(+) Bregs were evaluated in addition to their CD5(+) subsets in 69 patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5(+) CD24(hi) CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5(+) subset of CD24(hi) CD38(hi) B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5(+) B cells are enriched in the ability to produce IL-10 compared to CD5(neg) B cells. Together these results suggest that CD5 may identify functional IL-10-producing Bregs . The malfunction of Bregs during active disease due to reduced IL-10 expression may thus permit ANCA production.

Dermatofibroma with osteoclast-like giant cells.

Dermatofibroma (DF), or cutaneous fibrous histiocytoma, is a common cutaneous tumor with many variants that may arise from alterations in the morphology and composition of its various components. One type that has not received much attention is DF with osteoclast-like giant cells. Two cases of this rare tumor are described. The importance of this tumor lies in the possible histologic confusion with a variety of benign and malignant neoplasms, including giant cell tumor of tendon sheath, giant cell tumor of bone, and giant cell reparative granuloma.

Influence of omega-3 and omega-6 fatty acid sources on prostaglandin levels in mice.

Studies from this laboratory, employing a hairless mouse model, have indicated that a polyunsaturated fatty acid source rich in omega-3 (n-3) fatty acid (FA) inhibits ultraviolet (UV)-carcinogenic expression, when compared to that of diets containing predominantly n-6 fatty acids. Omega-3 FA is a poor substrate for cyclooxygenase, the rate-limiting step in prostaglandin (PG) synthesis--the latter, particularly PGE2, are known to influence tumor biology. Based upon this rationale, plasma and cutaneous PGE2 levels were determined from hairless mice fed diets containing either 4% or 12% corn or menhaden oil. After two weeks on the respective diets, plasma PGE2 levels of corn oil-fed animals were approximately 6-fold greater than those of the menhaden oil-fed groups. A similar response was found in the dermis. Although the relationship to carcinogenic expression is unknown, dietary n-3 FA content can have a pronounced effect upon PGE2 levels and possesses the potential for influencing other immunomodulators.

Simultaneously active lesions of vitiligo and erythema dyschromicum perstans.

Recently, a patient presented to us with skin that had areas of normal pigmentation, hyperpigmentation, and depigmentation. Workup eventually showed him to have simultaneously active lesions of a depigmenting disorder, vitiligo, and a hyperpigmenting disorder, erythema dyschromicum perstans.