Epidemiology, Treatment Patterns, and Healthcare Resource Utilization Study of Patients With Alopecia Areata in Taiwan's National Health Insurance Research Database.

OBJECTIVES: This study investigated the epidemiology, treatment patterns, and resource utilization in patients with alopecia areata (AA) in Taiwan using the National Health Insurance Research Database. AA severity was determined by treatment use and diagnostic codes in the year after enrollment (including corticosteroids, systemic immunosuppressants, topical immunotherapy, and phototherapy). METHODS: The cross-sectional analysis was conducted to estimate the incidence and prevalence of AA from 2016 to 2020. For the longitudinal analysis, 2 cohorts were identified: mild/moderate and severe. The cohorts were matched based on age, gender, and comorbidities. Patients were enrolled upon their first claim with an AA diagnosis during the index period of 2017-2018. RESULTS: The number of patients with AA increased from 3221 in 2016 to 3855 in 2020. The longitudinal analysis identified 1808 mild/moderate patients and 452 severe patients. Mild/moderate patients used higher levels of topical corticosteroids (82.41%) than severe patients (73.45%). Conversely, severe patients used more topical nonsteroids (41.81%) and systemic therapies (51.77%) than mild/moderate patients (0.44% and 16.15%, respectively). Oral glucocorticoids use was higher in severe patients (47.57%) relative to mild/moderate patients (14.88%), whereas the use of injectable forms was similar. The most used systemic immunosuppressants were methotrexate, cyclosporin, and azathioprine. Topical immunotherapy utilization decreased with subsequent treatment lines for severe patients. Treatment persistence at 6 months was low for all treatments. Severe patients had higher annual AA-related outpatient visits than the mild/moderate cohort. CONCLUSIONS: These findings highlight the need for additional innovations and therapies to address the clinical and economic burden of AA.

APRIL and BAFF promote increased viability of replicating human B2 cells via mechanism involving cyclooxygenase 2.

Of relevance to both protective and pathogenic responses to Ag is the recent finding that soluble molecules of the innate immune system, i.e., IL-4, B cell-activation factor of the TNF family (BAFF), and C3, exhibit significant synergy in promoting the clonal expansion of human B2 cells following low-level BCR ligation. Although IL-4, BAFF, and C3dg each contribute to early cell cycle entry and progression to S phase, only BAFF promotes later sustained viability of progeny needed for continued cycling. The present study sought to further clarify the mechanisms for BAFF's multiple functions. By comparing BAFF and a proliferation-inducing ligand (APRIL) efficacy at different stages in the response (only BAFF binds BR3; both bind transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag, the early role was attributed to BR3, while the later role was attributed to TACI/B cell maturation Ag. Importantly, BAFF- and APRIL-promoted viability of cycling lymphoblasts was associated with sustained expression of cyclooxygenase 2 (COX-2), the rate-limiting enzyme for PGE2 synthesis, within replicating cells. Supernatants of cultures with BAFF and APRIL contained elevated PGE2. Although COX-2 inhibitors diminished daughter cell viability, exogenous PGE2 (1-1000 nM) increased the viability and recovery of lymphoblasts. Increased yield of viable progeny was associated with elevated Mcl-1, suggesting that a BAFF/APRIL --> TACI --> COX-2 --> PGE2--> Mcl-1 pathway reduces activation-related, mitochondrial apoptosis in replicating human B2 cell clones.

Innate immunity and human B cell clonal expansion: effects on the recirculating B2 subpopulation.

Foci of autoantigen-specific B lymphocytes in nonlymphoid tissues have been associated with development of autoimmune disease. To better understand the genesis of such ectopic lymphoid tissue, this study investigated whether several B cell-tropic innate immune system molecules, known to be elevated in response to inflammatory stimuli, can cooperate in fostering the T cell-independent clonal expansion of mature human B2 cells under conditions of limiting BCR engagement. Notable synergy was observed between BCR coligation with the C3dg-binding CD21/CD19 costimulatory complex, B cell-activating factor belonging to the TNF family (BAFF), and IL-4 in generating B cell progeny with sustained CD86 and DR expression. The synergy was observed over a wide range of BCR:ligand affinities and involved: 1) cooperative effects at promoting early cell cycle progression and viability; 2) BCR:CD21 coligation-promoted increases in BAFF receptors that were highly regulated by IL-4; 3) reciprocal effects of IL-4 and BAFF at dampening daughter cell apoptosis typical of stimulation by BCR:CD21 and either cytokine alone; and 4) BAFF-sustained expression of antiapoptotic Mcl-1 within replicating lymphoblasts. The results suggest that significant clonal proliferation of recirculating B2 cells occurs upon limited binding to C3dg-coated Ag in an inflammatory in vivo milieu containing both BAFF and IL-4. When rare autoantigen-presenting B cells undergo such expansions, both B cell and T cell autoimmunity may be promoted.