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The Psoriasis Risk Allele HLA-C*06:02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis.

ABSTRACT: Pharyngeal tonsillitis is one of the most common upper respiratory tract infections, and group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffers from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic forms of this disease are not yet fully understood, but genetic predisposition has been suggested. A genetic association study using Illumina's Immunochip single-nucleotide polymorphism (SNP) array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. More than 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (odds ratio [OR], 3.7 to 4.7; P = 4.9 × 10-6 to 5.7 × 10-6). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (P = 4.8 × 10-4; OR, 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*57:01, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis (P = 3.2 × 10-4; OR, 6.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis.

SUBMITTER: Haapasalo K

PROVIDER: S-EPMC6204729 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The Psoriasis Risk Allele <i>HLA-C*06:02</i> Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis.

Haapasalo Karita K Koskinen Lotta L E LLE Suvilehto Jari J Jousilahti Pekka P Wolin Annika A Suomela Sari S Trembath Richard R Barker Jonathan J Vuopio Jaana J Kere Juha J Jokiranta T Sakari TS Saavalainen Päivi P

Infection and immunity 20180921 10

Pharyngeal tonsillitis is one of the most common upper respiratory tract infections, and group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffers from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic forms of this disease are not yet fully understood, but genetic predisposition has been suggested. A genetic association study using Illumina's Imm ...[more]

PMID: 30037793

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Project description:ImportancePrevious research showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis but consisted mostly of small (and sometimes inconclusive) cohort studies.ObjectiveTo assess whether HLA-C*06:02 status is associated with a differential response to ustekinumab therapy in patients with psoriasis through a systematic review and a meta-analysis of available data.Data sourcesA comprehensive search was conducted using MEDLINE, Embase, the Cochrane Library, Web of Science, and gray literature sources. Databases were searched from January 1, 2000, to May 14, 2018. Search strategies included terms and synonyms for psoriasis, HLA-C, and ustekinumab. Languages were restricted to English, French, German, and Dutch.Study selectionStudies were included if they reported the association between HLA-C*06:02 status and 75% improvement in Psoriasis Area and Severity Index (PASI75) response to ustekinumab therapy in patients with plaque psoriasis after 6 and/or 3 months of treatment. Randomized clinical trials and observational studies were included. Screening and selection were performed independently by 2 reviewers.Data extraction and synthesisHLA-C*06:02 genotype status and PASI75 response rates were extracted by 2 reviewers. Data were pooled using random-effects models. Heterogeneity was assessed using the τ2 and I2 statistic. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed.Main outcome and measureThe primary outcome was the risk difference of achieving PASI75 after 6 months of ustekinumab therapy between HLA-C*06:02-positive and HLA-C*06:02-negative patients.ResultsA total of 8 studies were reviewed; 1048 patients were included for meta-analyses, and 937 patients were included for the primary analysis of PASI75 response after 6 months of treatment. Random-effects meta-analysis showed a risk difference of 0.24 (95% CI, 0.14-0.35; P < .001) in favor of HLA-C*06:02-positive patients. The median PASI75 response rate in the HLA-C*06:02-positive group was 92% (pooled, 89%; range, 62%-98%). For HLA-C*06:02-negative patients, the median response rate was 67% (pooled, 62%; range, 40%-84%). Substantial heterogeneity may have been present, with an I2 of 82%.Conclusions and relevanceThe meta-analysis showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis. Although HLA-C*06:02-positive patients had high PASI75 response rates after 6 months, the PASI75 response rate was also high in the HLA-C*06:02-negative group. There appears to be no rationale for excluding patients from ustekinumab treatment based on a negative HLA-C*06:02 status.

Dataset Information

The Psoriasis Risk Allele HLA-C*06:02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis.

Publications

The Psoriasis Risk Allele <i>HLA-C*06:02</i> Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis.

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