BTNL2 gene G16071A SNP seems to be a predisposing factor for sarcoidosis except in Caucasian postmenopausal women with sarcoid uveitis in whom the GG genotype prevails.
Human leukocyte antigen (HLA)-DRB1*03 is over-represented in LS, and is associated with a good prognosis, whereas HLA-DRB1*15-positive patients have a more chronic course of sarcoidosis.
We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions.
Together, these studies reveal the presence of linked <i>in situ</i> recognition of vimentin by both T- and B-cells in HLA-DRB1*03<sup>+</sup> sarcoidosis patients, associated with a selective humoral immune response to the vimentin C-terminus.
In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution.
We have previously demonstrated that in our series HLADRB1* 03:01 and haplotype HLA-DRB1*04:01-DPB1*04:01 are associated with good prognosis sarcoidosis.
The meta-analysis indicated that BTNL2G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility.
Results of in silico binding analyses showed that DRB1*03:01 consistently demonstrated the highest binding affinities for six bacterial peptides previously found in sarcoidosis granulomas, whereas *12:01 displayed the lowest binding affinities.
The aim of this study was to further investigate associations between HLA-DRB1 alleles and the risk for extra-pulmonary manifestations (EPMs), i.e. engagement of the skin, superficial lymph nodes, eyes, nervous system, kidneys, hypercalcemia, parotid and salivary glands, heart, liver, spleen and bone marrow in Scandinavian sarcoidosis patients.
These results confirm the association of BTNL2 rs2076530SNP with the susceptibility to develop sarcoidosis, but not with an increased risk of cancer in these patients.
According to multivariate analysis (MVA), the presence of HLA DRB1*15 was indicated as an independent risk factor for sarcoidosis (OR:2.37; 95% CI: 1.31-4.30, p=0.004).
Both BTNL2 SNPs were associated with risk of sarcoidosis in separate models, but in a combined analysis the increased risk was due to the A-allele of the rs3817963 SNP; each copy of the A-allele was associated with a 40 % increase in risk of sarcoidosis (p = 0.02) and was confirmed by our haplotypic analysis.
Among sarcoidosis patients, the HLA A*23, A*80, B*08, B*41, DQB1*05 and DRB1*14 antigens tended to be more common than in the controls, whereas the B*44, B*45, B*51, B*58, DRB1*15 and DRB1*16 alleles were more frequently found in control subjects than in the sarcoidosis patients.
BTNL2 rs206530 A allele frequencies were significantly higher in sarcoidosiswith no linkage disequilibrium with HLA-DRB1 alleles, except in the subgroup of patients with Löfgren syndrome where the determinant allele was HLA-DRB1*03.
The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles.
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.