Objective. Although B cells are implicated in the pathogenesis of systemic lupus erythematosus, the role of B cell depletion (BCD) as a treatment is controversial, given the variable benefit in human disease. This study was undertaken to test the effects of BCD therapy in a murine lupus model to better understand the mechanisms, heterogeneity, and effects on disease outcomes.Methods. (NZB ؋ NZW)F 1 female mice with varying degrees of disease severity were treated with an anti-mouse CD20 (anti-mCD20) antibody (IgG2a), BR3-Fc fusion protein (for BAFF blockade), or control anti-human CD20 monoclonal antibody (ϳ10 mg/kg each). Tissue samples were harvested and analyzed by flow cytometry. The development and extent of nephritis were assessed by monitoring proteinuria (using a urine dipstick) and by immunohistochemical analysis of the kidneys. Serum immunoglobulin levels were measured by enzyme-linked immunosorbent assay.Results. After a single injection of anti-mCD20, BCD was more efficient in the peripheral blood, lymph nodes, and spleen compared with the bone marrow and peritoneum of normal mice as well as younger mice with lupus. Since depletion of the marginal zone and peritoneal B cells was incomplete and variable, particularly in older mice with established nephritis, a strategy of sequential weekly dosing was subsequently used, which improved the extent of depletion. BAFF blockade further enhanced depletion in the spleen and lymph nodes. Early BCD therapy delayed disease onset, whereas BCD therapy in mice with advanced disease reduced the progression of nephritis. These effects were long-lasting, even after B cell reconstitution occurred, and were associated with a reduction in T cell activation but no significant change in autoantibody production.Conclusion. The lasting benefit of a short course of BCD therapy in lupus-prone mice with an intact immune system and established disease highlights the validity of this treatment approach.Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple organ systems. The immunologic events triggering the onset of clinical manifestations have not been fully defined, but a central role of B cells in the pathogenesis of this disease has been established by studies performed in multiple laboratories, both in mice and in humans (1-3). Given the strong evidence supporting an abnormal B cell compartment in SLE, B cell depletion (BCD) therapy is being investigated as a potential treatment strategy. Several open-label studies, including our own, have demonstrated that BCD provides significant clinical benefit in SLE (4,5). Our studies have shown that clinical improvement after BCD therapy precedes the decline in levels of conventional serum autoantibodies, strongly supporting the notion of antibody-independent pathogenic roles of B cells.

Methylchloroisothiazolinone/methylisothiazolinone is a preservative found in cosmetic and industrial products, and is a common ingredient in moist toilet paper. It is a well-known allergen and is capable of causing allergic contact dermatitis.We present the case of a 58-year-old white woman with a cutaneous vulvar eruption with associated discomfort and pruritus of 6 months in duration. She had been treated with antibiotic and antifungal agents without improvement of symptoms. Careful history taking revealed that the patient was using moist toilet paper. Patch testing confirmed an allergy to methylchloroisothiazolinone, a preservative in the moist toilet paper. After discontinuation of the product and treatment with potent topical steroids, the eruption completely cleared.With the growing use of moist toilet paper among adults, the risk of exposure and potential sensitization is increasing. Health care providers should be aware of the risks of moist toilet paper containing potential allergens because perianal and perineal dermatitis caused by these products may be unrecognized or misdiagnosed. After proper treatment, patients must be educated about alternatives and the importance of label reading.

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RATIONALE: We present two patients with identical hemizygous IL2RG R222C mutations and variable clinical presentation. METHODS: Genetic sequencing identified the same hemizygous missense mutation (c.664C>T; p. R222C) in IL2RG. RESULTS: Patient 1 had TRECs of 8 on newborn screen (NBS) and a brother who died at 13-months-old from bronchopneumonia. The patient had a T-B+NK+ phenotype with T-cell lymphopenia (525 CD3 cells/mL, 193 CD4 cells/mL, (28 CD45RA+ and 138 CD45RO+) and 304 CD8 cells/ mL). He had slightly reduced proliferative responses to PHA and Con A and normal proliferation to PWM and tetanus. HLA typing revealed 3.2% maternal engraftment, which may account for the surprising finding of tetanus-induced lymphocyte proliferation. Patient 2 presented at 7-months-old with respiratory failure from PJP pneumonia. He had a normal NBS (TRECs of 28) and received routine vaccinations without incident, including rotavirus. Despite modest proliferation to mitogen stimulation correlating with modest lymphopenia (T-B+NK+ with 1702 CD3 cells/mL, 1204 CD4 cells/mL (583 CD45RA+ and 668 CD45RO+), and 470 CD8 cells/mL), he had no proliferation to tetanus and undetectable tetanus and diphtheria antibody titers. His poor proliferation to in vitro CD3 mAb stimulation plus cytokines (IL-7, IL-15, and IL-2) and absent tetanus-induced lymphocyte proliferation supported a hypomorphic/'leaky' SCID diagnosis. CONCLUSIONS: Reduced TREC content and marked na€ ıve T-cell lymphopenia do not consistently identify IL2RG R222C mutations; however, reduced T-cell proliferation following cytokine stimulation strongly suggests this diagnosis. These patients demonstrate the T-cell phenotypic variability that complicate the diagnosis of hypomorphic X-linked SCID. Another diagnostic challenge is that maternal engrafted T cells may mediate antigen-specific vaccine responses.