HLA-DRB1* alleles and symptoms associated with Heerfordt's syndrome in sarcoidosis

Abstract

Heerfordt's syndrome (HS) consists in its complete form of uveitis, parotid or salivary gland enlargement and cranial nerve palsy. The objective of the present study was to analyse if there are also links between HLA-DRB1* alleles and HS, as it is a specific phenotype of sarcoidosis.1,000 patients with sarcoidosis, out of whom 83 had symptoms associated with HS, were included in the study together with a group of 2,000 healthy individuals from the same population, matched for sex and age. HLA-DRB1* allelic groups were determined for all individuals, and comparisons were made between different disease subgroups and between patients and healthy controls.We found that the HLA-DRB1*04 allele was overrepresented in patients with symptoms associated with HS. 83 (8.3%) of all patients had one or more of the symptoms and 46 (55%) of them were HLA-DRB1*04 positive. 44 (55%) of the patients with ocular sarcoidosis, i.e. the most common symptom associated with HS, were HLA-DRB1*04 positive, compared with 35.9% of healthy controls (p50.0008), and only 26.6% of the whole group of sarcoidosis patients (p,0.0001).HLA-DRB1*04 seems to protect against overall sarcoidosis but appears to be a significant risk factor for ocular sarcoidosis as well as for other manifestations associated with HS.

Major histocompatibility complex class II andBTNL2associations in sarcoidosis

“…Previously, HLA-DRB1*04 has been proposed to associate with Heerfordt's syndrome, uveitis and ocular sarcoidosis [2,9,10], but no association with HLA-DRB1*04:01 and the disease course of sarcoidosis has been published. In our study the frequency of haplotype DRB1*04:01-DPB1*04:01 was increased in resolved sarcoidosis when compared with the controls (16.9% versus 7.3%; p50.02, OR 2.6, 95% CI 1.12-5.86) or persistent sarcoidosis (16.9% versus 6.1%; p50.02, OR 3.1, 95% CI 1.15-8.41).…”

Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans

“…The strongest genetic associations with sarcoidosis are found in the HLA class II region of Chromosome 6p; among these genes, HLA-DRB1 is the most widely validated, with numerous associated risk variants (3)(4)(5)(6)(7)(8)(9)(10)(11). In the United States, African Americans suffer disproportionately from higher sarcoidosis prevalence and from more severe disease (12)(13)(14).…”

Update on sarcoidosis

“…The presence of the HLADRB1 Ã 11 impacted the clinical phenotype and was identified more frequently in patients without extra-pulmonary findings [25]. The allele DRB1 Ã 0401 was highly associated with sarcoidosis with ocular involvement [26].…”