Does the shared epitope genotype influence either the susceptibility to or the phenotype of corneal melting?
OBJECTIVE
To investigate the role of the shared epitope alleles in determining susceptibility to and the phenotype of corneal melting in patients with rheumatoid arthritis (RA).


METHODS
The HLA class 1 and 2 genotype was determined for 17 patients with rheumatoid-associated comeal melting by the phototyping method. HLA-DR4 subtyping was performed by PCR sequence-based typing. The frequency of all the shared epitope alleles and, in particular, of the higher-risk *0401 and *0404 alleles, was compared with healthy controls and unrelated RA patients, with and without extra-articular manifestations. A comparison was also made between the shared epitope genotype of the corneal melt patients and local, ocular disease characteristics.


RESULTS
Thirteen (76%) patients with corneal melt possessed at least one shared epitope allele and 5 (29%) possessed two alleles. The dominant alleles were variants of the DR4 family, notably the *0401, *0404 and *0408 alleles. Both the allele frequency and a double dose of shared epitope alleles were more common in the three RA patient groups than in the healthy, control group (p < 0.005). Although the frequency of the higher-risk alleles was similar in the three RA patient group, a trend existed for a double dose of higher-risk alleles to be more common in the patients with either corneal melt or other extra-articular manifestations (p > 0.2). No association was found between the number or type of shared epitope alleles and any of the ocular disease characteristics studied.


CONCLUSIONS
The results of this study suggest that the shared epitope alleles do not influence the ocular disease phenotype of corneal melt in RA patients. Shared epitope determination of RA patients may help to identify those susceptible to either corneal melt or other extra-articular disease. RA patients with a double dose of higher-risk alleles may have an increased risk of corneal melt.
McKibbin
M
M
Department of Ophthalmology, St James's University Hospital, Leeds, UK. martinmckibbin@cswebmail.com
Clark
B
B
Isaacs
J D
JD
Morrell
A J
AJ
Griffiths
B
B
Morgan
A W
AW
Gooi
H C
HC
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics* / Q000276:immunology; D003320:Corneal Ulcer / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D010641:Phenotype
D015804:HLA-DR4 Antigen