Mutations in the scaffolding domain of Receptor Interacting Protein kinases (RIP) underlie the recently described human autoimmune syndrome, CRIA, characterized by lymphadenopathy, splenomegaly, and autoantibody production. While disease mechanisms for CRIA remain undescribed, RIP kinases work together with caspase-8 to regulate cell death, which is critical for normal differentiation of many cell types. Here, we describe a key role for RIP1 in facilitating innate B cell differentiation and subsequent activation. By comparing RIP1, RIP3, and caspase-8 triple deficient and RIP3, caspase-8 double deficient mice, we identified selective contributions of RIP1 to an accumulation of murine splenic Marginal Zone (MZ) B cells and B1-b cells. We used mixed bone-marrow chimeras to determine that innate B cell commitment required B cell-intrinsic RIP1, RIP3, and caspase-8 sufficiency. RIP1 regulated MZ B cell development rather than differentiation and RIP1 mediates its innate immune effects independent of the RIP1 kinase domain. NP-KLH/alum and NP-Ficoll vaccination of mice doubly deficient in both caspase-8 and RIP3 or deficient in all three proteins (RIP3, caspase-8, and RIP1) revealed uniquely delayed T-dependent and T-independent IgG responses, abnormal splenic germinal center architecture, and reduced extrafollicular plasmablast formation compared to WT mice. Thus, RIP kinases and caspase-8 jointly orchestrate B cell fate and delayed effector function through a B cell-intrinsic mechanism.

Background Alopecia reduces perceptions of age, beauty, success, and adaptability. Hair loss can be caused by genetic, physiological, environmental, and immunologic factors. The current treatment for alopecia is varied. This systematic review and meta-analysis evaluates activated platelet rich plasma (A-PRP) for alopecia treatment. Objectives The objective of this review was to assess the clinical efficacy and safety of autologous activated PRP (A-PRP) injections in alopecia patients. We compare the safety, limitations, and outcomes of A-PRP use with those of prior research on alopecia. Methods We searched PubMed, EMBASE, the Cochrane Database, and Google Scholar for relevant articles. We included all primary clinical studies involving patients that evaluated A-PRP. Results Twenty-nine articles met the eligibility criteria, which included 864 patients, and were analyzed for qualitative review. Our review found that 27 studies indicated that A-PRP is significantly effective in treating alopecia, especially for improving hair density before and after therapy (n = 184, MD = 46.5, I2 = 88%, 95% CL 29.63–63.37, P 0.00001) as well as when comparison is made between treatment and control group (n = 88, MD = 31.61, I2 = 80%, 95% CI: 6.99-56.22, P = 0.01); terminal hair density between treatment and control group (n = 55, MD = 26.03, I2 = 25%, 95% CI 8.08-43.98, P = 0.004); hair counts after therapy (n = 85, MD = 12.79, I2 = 83%, 95% CI -5.53, 31.12, P = 0.0006); promoting hair regrowth; folliculogenesis; reducing hair loss; combining with FUs surgery; and initiating the hair cycle. Two studies did not report significant results. Conclusions This is the first systematic review and meta-analysis of A-PRP as a treatment option for alopecia. A-PRP appears to be a promising and safe method for treating alopecia.

Objective. Microtia is a congenital condition known to be associated with vertebral anomalies and congenital syndromes, most prominently hemifacial microsomia. There is controversy, however, on whether to screen with spinal imaging. Additionally, microtia ear reconstruction utilizes rib harvesting that could potentially worsen pre-existing vertebral and rib anomalies, specifically scoliosis. We report on the prevalence and characteristics of vertebral anomalies among microtia patients at a tertiary pediatric center.Study Design. Retrospective case review with literature review.Setting. Tertiary pediatric referral center.Methods. A review of 425 children with microtia was conducted, characterized as either syndromic or nonsyndromic. Data included demographics, spinal imaging performed, indications, anomalies detected, and microtia repair.Results. Among 425 microtia patients, 24.5% were syndromic with an average age of 9.7 years. Only 18.4% of all patients had spinal imaging performed (50% syndromic vs 8.1% nonsyndromic). Overall, 10.6% had a vertebral anomaly with a 57.7% detection rate (67.3% syndromic vs 38.5% nonsyndromic). The most common anomaly was scoliosis, with a prevalence of 7.8%. Fusion defects and rib deformities were the next most prominent. Microtia repair, most commonly with an autologous rib graft, was performed in 21.6% of the cohort. However, only 19.2% had spinal imaging and 16.7% with a vertebral anomaly. Conclusion.Children with microtia are at a greater risk of vertebral abnormalities. Scoliosis prevalence in isolated microtia is comparable to the general population (2%-3%) but greatly increased with genetic syndromes. Screening for vertebral anomalies should be considered when planning microtia reconstructions, especially in the syndromic population.

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