Exploring causal correlations between inflammatory proteins and Bullous
pemphigoid:bi-directional mendelian randomisation study
Abstract
Bullous pemphigoid (BP), the most common autoimmune bullous disease,
typically presents with generalized crops of tense, pruritic cutaneous
blisters and mostly affects the elderly, Here, we aimed to figure out
the interplay between peripheral inflammatory proteins and BP. Based on
publicly available genetic data, bidirectional Mendelian randomization
(MR) analysis was performed to determine the causal association between
91 inflammatory proteins and BP. The inverse-variance weighted (IVW)
method was used as the primary MR method to estimate causal effects,
while MR-Egger, weighted mode methods, weighted median, and simple mode
were performed to explore the causal association. The leave-one-out
(LOO) analysis, MR pleiotropy residual sum, and Cochran’s Qtest were
used to exclude possible horizontal pleiotropic outliers and verify the
robustness, heterogeneity, and horizontal pleiotropy of the results. The
results indicated that 2 inflammatory proteins associated with the risk
of BP were identified, These are Macrophage Inflammatory Protein 1a
(MIP-1a) [IVW OR = 1.69, 95% CI = 1.00-2.84, p = 0.048] with a
total of 6 SNPs and Leukemia Inhibitory Factor Receptor (LIFR) [IVW OR
= 1.34, 95% CI = 0.24-0.93, p = 0.029] with 3 SNPs. In addition,
Fractalkine levels [IVW OR = 0.99, 95% CI = 0.98-1.00, p=0.033] was
suggested to be the consequences of BP,Sensitivity analysis further
excluded the influence of heterogeneity and horizontal pleiotropy. This
study suggested that MIP-1a and LIFR were positively associated with the
risk of BP, while the LIFR was negatively associated with the risk of BP
,besides,the Fractalkine levels is more likely to be involved in BP
development downstream,which furthers our understanding of immune cells
in the pathogenesis of BPand contributes to the study of accurate
treatment.