Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Increase of KL-6 in sera of uveitis patients with sarcoidosis.

BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. METHODS: Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. RESULTS: The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). CONCLUSION: Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.