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Amino Acid Residue 67 (Isoleucine) of HLA-DRB Is Associated with POHS

¹ From the Department of Ophthalmology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands; the ² Departments of Molecular and Immunopathology and ³ Ophthalmology, University Medical Centre Utrecht, Utrecht, The Netherlands; the ⁴ Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands; and the ⁵ Department of Ophthalmology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

PURPOSE. To investigate whether presumed ocular histoplasmosis syndrome (POHS) in The Netherlands is associated with HLA-DR2 and HLA-B7, as previously shown in the United States.

METHODS. Twenty-four Dutch patients with POHS were included in this study. DNA isolated from peripheral blood leukocytes was typed for HLA by a sequence-based method. Associations were statistically determined. The frequencies of HLA alleles in bone marrow of donors listed on the European donor registry was used to represent the distribution in the normal population. Patients were included in the study only when no cells were present in the vitreous at any time and when fundus photographs fit the diagnosis made according to the following criteria: presence of peripapillary atrophy, presence of punched out chorioretinal lesions (histospots), and presence of a submacular scar. After the fundus photographs were judged, the patients were divided into two groups. Group1 contained patients who met all three diagnostic criteria (complete POHS), and group 2 contained patients who met one or two of the criteria (incomplete POHS).

RESULTS. Group 1 consisted of 14 patients and group 2 of 10 patients. An association between POHS and HLA-DR2 and -B7 was present, compared with the normal Dutch control subjects. Although significant, the association between the frequency of HLA-DR2 and -B7 of all patients with POHS was less striking than the findings in patients with POHS in the United States. The association with DR2 in patients with incomplete POHS (group 2) was significantly different from that in the group with complete POHS (group 1). According to the defined criteria the association of POHS with HLA-B7 and -DR2 was confined to the incomplete POHS group and was not found in the complete POHS group. Furthermore, analysis of DR at the amino acid level, rather than at the allele level (DR2) showed that amino acid 67 of the DRB1 alleles had the most significant HLA association with POHS, independent of the two groups.

CONCLUSIONS. POHS in Dutch patients was associated with HLA-B7 and -DR2, but more striking was the presence of isoleucine at position 67 of the HLA-DR molecule.