Neutrophilic urticaria with systemic inflammation: a case series.

IMPORTANCE: Predominantly neutrophilic infiltrates are seen in a subset of patients with urticaria. The lesions tend to be less itchy and poorly responsive to standard therapy, including antihistamines. We describe 2 patients having neutrophilic urticaria with systemic inflammation (NUSI) without known connective tissue disorder or malignancy. We propose the term NUSI to help classify a previously undefined multisystemic inflammatory entity likely mediated by interleukin 1 (IL-1). OBSERVATIONS: Patient 1, a 47-year-old woman, was seen with urticaria and associated night sweats, fevers, and polyarticular arthritis. Acute-phase reactants were elevated with worsening of symptoms. Initial treatment with a combination of topical and systemic corticosteroids, antihistamines, and immunosuppressants was unsuccessful. A 100% clinical resolution was achieved with anakinra, an IL-1 receptor antagonist. Patient 2, a 24-year-old woman, was seen with urticaria and associated joint pain and swelling. Initial treatment included a combination of antihistamines, colchicine, and dapsone. Only colchicine provided moderate benefit but was stopped because of significant gastrointestinal tract discomfort. Anakinra was initiated; the patient achieved 100% control while receiving daily therapy. CONCLUSIONS AND RELEVANCE: The diagnosis of NUSI is important to consider in patients who are seen with antihistamine-resistant urticaria in combination with systemic inflammatory symptoms. Interleukin 1 blockade is a viable option for therapy.

Higher CD27+CD8+ T cells percentages during suppressive antiretroviral therapy predict greater subsequent CD4+ T cell recovery in treated HIV infection.

HIV-mediated immune dysfunction may influence CD4(+) T cell recovery during suppressive antiretroviral therapy (ART). We analyzed cellular biomarkers of immunological inflammation, maturation, and senescence in HIV-infected subjects on early suppressive ART. We performed longitudinal analyses of peripheral immunological biomarkers of subjects on suppressive ART (n = 24) from early treatment (median 6.4 months, interquartile range [IQR] 4.8-13.9 months) to 1-2 years of follow-up (median 19.8 months, IQR 18.3-24.6 months). We performed multivariate regression to determine which biomarkers were associated with and/or predictive of CD4(+) T cell recovery. After adjusting for the pre-ART CD4(+) T cell count, age, proximal CD4(+) T cell count, and length of ART medication, the percentage of CD27(+)CD8(+) T cells remained significantly associated with the CD4(+) T cell recovery rate (ß = 0.092 cells/ul/month, P = 0.028). In HIV-infected subjects starting suppressive ART, patients with the highest percentage of CD8(+) T cells expressing CD27 had the greatest rate of CD4(+) T cell recovery.

A functional variant in FCRL3 is associated with higher Fc receptor-like 3 expression on T cell subsets and rheumatoid arthritis disease activity.

OBJECTIVE: CD4+FoxP3+ Treg cells suppress effector T cells and prevent autoimmune disease. Treg cell function is deficient in active rheumatoid arthritis (RA), a loss which may play a role in the pathogenesis of this disease. We previously showed that a single-nucleotide polymorphism in the FCRL3 gene led to higher expression of Fc receptor-like 3 (FcRL3) on Treg cells and that FcRL3+ Treg cells are functionally deficient in comparison to FcRL3- Treg cells. This study was undertaken to investigate the potential role of FcRL3 in RA. METHODS: A cross-sectional study was performed to evaluate the FCRL3 -169 genotype and FcRL3 expression on T cell subsets, including Treg cells, in peripheral blood samples from 51 patients with RA enrolled in the University of California, San Francisco (UCSF) RA Cohort. Clinical data were obtained from the UCSF RA Cohort database. RESULTS: Patients with the FCRL3 -169C allele (genotype C/C or C/T) expressed higher levels of FcRL3 on Treg cells, and on CD8+ and γ/δ T cells, in comparison to RA patients with the T/T genotype. Higher FcRL3 expression on these T cell subpopulations correlated with RA disease activity in patients harboring the FCRL3 -169C allele. Furthermore, FcRL3 expression on Treg cells was higher in patients with erosive RA, and the FCRL3 -169C allele was overrepresented in patients with erosive RA. CONCLUSION: Our findings indicate that FcRL3 expression, which is strongly associated with the presence of the FCRL3 -169C allele, may serve as a biomarker for RA disease activity.

Expression of the autoimmune susceptibility gene FcRL3 on human regulatory T cells is associated with dysfunction and high levels of programmed cell death-1.

CD4(+)FoxP3(+) regulatory T cells (T(reg)) play a critical role in maintaining self-tolerance and inhibiting autoimmune disease. Despite being a major focus of modern immunological investigation, many aspects of T(reg) biology remain unknown. In a screen for novel candidate genes involved in human T(reg) function, we detected the expression of an autoimmune susceptibility gene, FcRL3, in T(reg) but not in conventional CD4(+) T cells. FcRL3 is an orphan receptor of unknown function with structural homology to classical Fc receptors. Numerous genetic studies have demonstrated a link between a single nucleotide polymorphism in the FCRL3 promoter and both overexpression of FcRL3 and autoimmune diseases such as rheumatoid arthritis. Given the critical role of T(reg) in suppressing autoimmunity, we sought to ascertain how expression of FcRL3 relates to the phenotype, differentiation, and function of T(reg). We show in this study that FcRL3 is expressed on a population of thymically derived T(reg) that exhibits a memory phenotype and high levels of programmed cell death-1. Purified FcRL3(+) T(reg) are less responsive to antigenic stimulation in the presence of IL-2 than their FcRL3(-) counterparts, despite intact proximal and distal IL-2 signaling as determined by phosphorylation of Stat-5 and upregulation of Bcl2. In vitro suppression assays demonstrated that FcRL3(+) T(reg) have reduced capacity to suppress the proliferation of effector T cells. These data suggest that FcRL3 expression is associated with T(reg) dysfunction that may, in turn, contribute to the loss of self-tolerance and the development of autoimmunity.