Coexistence of bullous pemphigoid with neuropsychiatric comorbidities is associated with anti‐BP230 seropositivity

Abstract

Background While clustering of bullous pemphigoid (BP) with neuropsychiatric diseases is well‐established, the clinical and immunological profile of BP patients with this comorbidity remains to be decisively determined. Objectives To evaluate the burden of neurological and psychiatric comorbidities among patients with BP and to elucidate the clinical, immunological and immunopathological features of patients with BP and comorbid neuropsychiatric conditions. Methods We performed a retrospective study encompassing patients diagnosed with BP throughout the years 2009–2020 in a specialized tertiary referral centre. Multivariate logistic regression model was used to identify predictors of neuropsychiatric conditions among patients with BP. Results The study included 273 patients with BP, of whom 123 (45.1%) presented with comorbid neuropsychiatric disease. Compared to the remaining patients with BP (n = 150), those with pre‐existing neuropsychiatric diseases demonstrated older mean [standard deviation (SD)] age [81.7 (9.1) vs. 76.9 (10.1); P < 0.001], female preponderance (65.0% vs. 49.3%; P = 0.009), higher seropositivity rate of anti‐BP230 (67.7% vs. 36.5%; P = 0.006) and higher levels of anti‐BP180 NC16A IgG [651.3 (1279.6) vs. 370.4 (818.6) U/mL; P = 0.039]. In multivariate analysis, anti‐BP230 seropositivity was independently associated with coexistence of BP with neuropsychiatric conditions [adjusted odds ratio (OR), 3.43; 95% CI, 1.24–9.52; P = 0.018]. In a sensitivity analysis confined to patients with neurological diseases (n = 103), older age [82.1 (8.4) vs. 77.2 (10.3); P < 0.001] and increased anti‐BP230 seropositivity (68.0% vs. 39.7%; P = 0.018) were identified. Conclusions The coexistence of BP with neuropsychiatric diseases is independently associated with the generation of anti‐BP230 antibodies.

Association between bullous pemphigoid and psychiatric disorders: A systematic review and meta‐analysis

“…Bullous pemphigoid230 subtypes, including BPAG1a1 and BPAG1a2, were expressed in both peripheral and central nervous systems. Seropositivity of BP230 was found to be a predictor of neuropsychiatric comorbid diseases in patients with BP [33]. With respect to BP180, apart from the skin tissue, the presence of type XVII collagen was also found in human cortical, hippocampal, and amygdaloid neurons [34].…”

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study

“…In these studies, high serum anti‐BP180 IgG levels at the time of diagnosis were indicative for an early death and a higher number of infections 41–44 . In contrast, lower serum anti‐BP180 IgG levels were described in DPP4 inhibitor‐associated BP, 45,46 whereas BP230 reactivity was linked with neuropsychiatric comorbidities 47 …”

“…[41][42][43][44] In contrast, lower serum anti-BP180 IgG levels were described in DPP4 inhibitor-associated BP, 45,46 whereas BP230 reactivity was linked with neuropsychiatric comorbidities. 47 The aim of the present study was to explore the association of autoantibody reactivities with comorbidities and the medication of BP patients in a large multicentric cohort. Therefore, data on comorbidities and concomitant medication were collected prospectively in a large cohort of patients diagnosed on wellestablished criteria in 16 dermatological referral centers for autoimmune blistering diseases from six European countries.…”

Deciphering the Contribution of BP230 Autoantibodies in Bullous Pemphigoid

“…Using multivariate analysis, a large retrospective study of 273 BP patients showed that the presence of anti-BP230 antibodies, in addition to other variables, such as older age and female sex, was associated with the coexistence of neuropsychiatric disorders. After adjusting for confounders, anti-BP230 seropositivity proved to be the only independently significant predictor for comorbidity of neuropsychiatric diseases, such as dementia, epilepsy, multiple sclerosis, depression, and bipolar disorder in BP patients [ 64 ]. In another smaller study, BP patients with a comorbid neurological disease were found to have higher levels of both BP180 and BP230 autoantibodies, with a higher seropositivity rate for BP230 [ 65 ].…”