<b><i>Background:</i></b> Bright light therapy (BLT) has been used as a treatment for seasonal affective disorder (SAD) for over 30 years. This meta-analysis was aimed to assess the efficacy of BLT in the treatment of SAD in adults. <b><i>Method:</i></b> We performed a systematic literature search including randomized, single- or double-blind clinical trials investigating BLT (≥1,000 lx, light box or light visor) against dim light (≤400 lx) or sham/low-density negative ion generators as placebo. Only first-period data were used from crossover trials. The primary outcome was the post-treatment depression score measured by validated scales, and the secondary outcome was the rate of response to treatment. <b><i>Results:</i></b> A total of 19 studies finally met our predefined inclusion criteria. BLT was superior over placebo with a standardized mean difference of –0.37 (95% CI: –0.63 to –0.12) for depression ratings (18 studies, 610 patients) and a risk ratio of 1.42 (95% CI: 1.08–1.85) for response to active treatment (16 studies, 559 patients). We found no evidence for a publication bias, but moderate heterogeneity of the studies and a moderate-to-high risk of bias. <b><i>Conclusions:</i></b> BLT can be regarded as an effective treatment for SAD, but the available evidence stems from methodologically heterogeneous studies with small-to-medium sample sizes, necessitating larger high-quality clinical trials.

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Biallelic mutations in the human lipopolysaccharide responsive beige-like anchor (LRBA) gene lead to a primary immunodeficiency known as LRBA deficiency, characterized by a broad range of clinical manifestations including autoimmunity, organomegaly, hypogammaglobulinemia and recurrent infections. Considering the phenotypic heterogeneity in patients and the severity of the disease, our aim was to assess the role of LRBA in immune cells and to understand the underlying pathomechanisms through the study of a Lrba knockout (Lrba) mouse model. LRBA-deficient mice did not show severe clinical or immunological signs of disease, either at steady state under specific-pathogen-free conditions, after vaccination with T-dependent and T-independent antigens, or in the context of acute infections with lymphocytic choriomeningitis virus (LCMV) or Salmonella Typhimurium. Although Lrba mice were able to produce normal serum immunoglobulin M (IgM) and IgG and to mount a specific immune response after immunization, they showed elevated serum and secretory basal IgA levels. LRBA was dispensable for B- and T-cell development, as well as for in vitro B-cell proliferation, survival, isotype switching and plasmablast differentiation. Interestingly, Lrba mice displayed decreased cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression by regulatory T cells and activated conventional CD4 and CD8 T lymphocytes, reduced frequency of peritoneal B-1a cells along with diminished interleukin-10 production and increased percentages of T follicular helper cells in Peyer's patches, but without developing overt signs of autoimmunity. Our findings expand the role of LRBA in immune regulatory mechanisms previously reported in patients, and suggest a novel role in IgA production that is crucial for the protection of mucosal surfaces and gut-associated immune tolerance.