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Meta-Analysis
. 2024 Jan-Dec:38:3946320241296903.
doi: 10.1177/03946320241296903.

Association of HLA class II alleles and haplotypes with bullous and mucus membrane pemphigoid risk: A systematic review, a meta-analysis and a meta-regression

Tarak Dhaouadi  1 , Awatef Riahi  1 , Taïeb Ben Abdallah  1 , Yousr Gorgi  1 , Imen Sfar  1
Affiliations
Meta-Analysis

Association of HLA class II alleles and haplotypes with bullous and mucus membrane pemphigoid risk: A systematic review, a meta-analysis and a meta-regression

Tarak Dhaouadi et al. Int J Immunopathol Pharmacol. 2024 Jan-Dec.

Abstract

Although, several studies have assessed the association of HLA Class II and genes with bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), results were inconsistent and between-studies heterogeneity needs to be investigated. An electronic literature search for eligible studies among all papers published prior to May 31, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the three following HLA genes: DRB1, DQA1 and DQB1. Combined analyses revealed a significant increase in pemphigoid risk conferred by the following alleles: DQB1*0301, DRB1*11, DRB1*1101 subtype and DQA1*0505, all p-values <.001. However, there was a moderate to high level of between-studies heterogeneity. Subgroup analyses revealed that the risk conferred by the aforementioned alleles was significantly higher in case of dipeptidyl peptidase-4 inhibitors induced BP (DBP) comparatively to idiopathic BP and MMP. In addition, the risk conferred by the DQB1*0301 was significantly higher in MMP (OR [95% CI] = 5.25 [4.03-6.84]) than in BP (OR [95% CI] = 2.22 [1.87-2.65]), p = .007. Besides, the DRB1*1101-DQB1*0301 and DRB1*11-DQA1*05-DQB1*0301 haplotypes were significantly associated with an increased pemphigoid risk, both p-values <.001. Conversely, the DQA1*0201 allele was significantly associated with reduced pemphigoid risk (OR [95% CI] = 0.3 [0.17-0.52]), with no between-studies heterogeneity (I2 = 0%, p = .76). This meta-analysis demonstrated that the DRB1*1101, DQA1*0505 and DQB1*0301 were significantly associated with increased pemphigoid risk. These associations were found to be significantly stronger in case of DBP comparatively to idiopathic pemphigoid. The DQA1*0201 allele seems to play a protective role against pemphigoid. Registration: This review has been registered on PROSPERO: CRD42024552821, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024552821.

Keywords: HLA class II; bullous pemphigoid; haplotype; meta-analysis; meta-regression; mucous membrane pemphigoid.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram for study selection.
Figure 2.
Figure 2.
Summary of study risk of bias.
Figure 3.
Figure 3.
Forest plot for the association between the HLA-DQB1*0301 allele and pemphigoid risk.
Figure 4.
Figure 4.
Subgroup analysis by ethnicity for the HLA-DQB1*0301 allele.
Figure 5.
Figure 5.
Subgroup analysis by pemphigoid subtype for the HLA-DQB1*0301 allele.
Figure 6.
Figure 6.
Forest plot for the association between the HLA-DRB1*11 allele and pemphigoid risk.
Figure 7.
Figure 7.
Subgroup analysis by ethnicity for the HLA-DRB1*11 allele.
Figure 8.
Figure 8.
Subgroup analysis by pemphigoid subtype for the HLA-DRB1*11 allele.
Figure 9.
Figure 9.
Forest plot for the association between the HLA-DRB1*1101 subtype and pemphigoid risk.
Figure 10.
Figure 10.
Subgroup analysis by pemphigoid subtype for the HLA-DRB1*1101 subtype.
Figure 11.
Figure 11.
(a) Forest plot for the association between the HLA-DQA1*0505 allele and pemphigoid risk. (b) Forest plot for the association between the HLA-DQA1*0201 and pemphigoid risk.
Figure 12.
Figure 12.
(a) Forest plot for the association between the HLA-DRB1*1101-DQB1*0301 haplotype and pemphigoid risk. (b) Forest plot for the association between the HLA-DRB1*11-DQA1*05-DQB1*0301 haplotype and pemphigoid risk.
Figure 13.
Figure 13.
Subgroup analysis by ethnicity for the HLA-DRB1*1101-DQB1*0301 haplotype.
Figure 14.
Figure 14.
Subgroup analysis by pemphigoid subtype for the HLA-DRB1*1101-DQB1*0301 haplotype.
Figure 15.
Figure 15.
Funnel plots assessing publication bias: Symmetrical funnel plots with no evidence of publication biases. (a) HLA-DQB1*0301 allele. (b) HLA-DRB1*11 allele. (c) HLA-DRB1*11 subtype. (d) HLA-DQA1*0505 allele. (e) HLA-DQA1*0201 allele. (f) HLA-DRB1*1101-DQB1*0301 haplotype. (g) HLA-DRB1*11-DQA1*05-DQB1*0301 haplotype.
See this image and copyright information in PMC

References

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