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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1997 Aug;56(8):488–492. doi: 10.1136/ard.56.8.488

The LMP2 polymorphism is associated with susceptibility to acute anterior uveitis in HLA-B27 positive juvenile and adult Mexican subjects with ankylosing spondylitis

W Maksymowych 1, G Jhangri 1, C Gorodezky 1, M Luong 1, C Wong 1, R Burgos-Vargas 1, M Morenot 1, J Sanchez-Corona 1, C Ramos-Remus 1, A Russell 1
PMCID: PMC1752428  PMID: 9306872

Abstract

INTRODUCTION—An association between polymorphism of the HLA linked LMP2 locus and the development of acute anterior uveitis (AAU) has previously been described in B27 positive white subjects with ankylosing spondylitis (AS). This study evaluated LMP2 alleles in two HLA-B27 positive Mexican populations of patients with spondyloarthropathy known to have a different clinical spectrum of disease from white people.
PATIENTS AND METHODS—The study populations consisted of 90 AS patients from Guadalajara with predominantly adult onset disease and 80 AS patients from Mexico City with predominantly juvenile onset disease. LMP2-CfoI amplified fragment length polymorphisms were determined after polymerase chain reaction amplification and digestion with CfoI restriction enzyme.
RESULTS—There was an increased LMP2A allelic frequency in patients who had had AAU in both Guadalajara (31.8%) and Mexico City (33.3%) when compared with non-AAU patients (15.2% and 17.7% of Guadalajara and Mexico City populations, respectively). The odds ratio relating LMP2A allelic frequency and AAU for the combined population, stratified by age at onset of disease, was 2.51 (p=0.01). LMP2 alleles did not influence the age at onset of disease or the development of peripheral arthritis.
CONCLUSIONS—These data support the view that polymorphism at the LMP2 locus is associated with the development of AAU in B27 positive subjects with AS. The requirement for both the less common LMP2 allele and HLA-B27 is consistent with the low prevalence of AAU in Mexican patients with spondyloarthritis.



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Selected References

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  1. Aki M., Shimbara N., Takashina M., Akiyama K., Kagawa S., Tamura T., Tanahashi N., Yoshimura T., Tanaka K., Ichihara A. Interferon-gamma induces different subunit organizations and functional diversity of proteasomes. J Biochem. 1994 Feb;115(2):257–269. doi: 10.1093/oxfordjournals.jbchem.a124327. [DOI] [PubMed] [Google Scholar]
  2. Brown M. A., Pile K. D., Kennedy L. G., Calin A., Darke C., Bell J., Wordsworth B. P., Cornélis F. HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom. Ann Rheum Dis. 1996 Apr;55(4):268–270. doi: 10.1136/ard.55.4.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burgos-Vargas R., Clark P. Axial involvement in the seronegative enthesopathy and arthropathy syndrome and its progression to ankylosing spondylitis. J Rheumatol. 1989 Feb;16(2):192–197. [PubMed] [Google Scholar]
  4. Burgos-Vargas R., Naranjo A., Castillo J., Katona G. Ankylosing spondylitis in the Mexican mestizo: patterns of disease according to age at onset. J Rheumatol. 1989 Feb;16(2):186–191. [PubMed] [Google Scholar]
  5. Burgos-Vargas R., Vázquez-Mellado J. The early clinical recognition of juvenile-onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis. Arthritis Rheum. 1995 Jun;38(6):835–844. doi: 10.1002/art.1780380618. [DOI] [PubMed] [Google Scholar]
  6. Burney R. O., Pile K. D., Gibson K., Calin A., Kennedy L. G., Sinnott P. J., Powis S. H., Wordsworth B. P. Analysis of the MHC class II encoded components of the HLA class I antigen processing pathway in ankylosing spondylitis. Ann Rheum Dis. 1994 Jan;53(1):58–60. doi: 10.1136/ard.53.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Calin A., Marder A., Becks E., Burns T. Genetic differences between B27 positive patients with ankylosing spondylitis and B27 positive healthy controls. Arthritis Rheum. 1983 Dec;26(12):1460–1464. doi: 10.1002/art.1780261207. [DOI] [PubMed] [Google Scholar]
  8. Dominguez O., Coto E., Martinez-Naves E., Choo S. Y., López-Larrea C. Molecular typing of HLA-B27 alleles. Immunogenetics. 1992;36(5):277–282. doi: 10.1007/BF00215655. [DOI] [PubMed] [Google Scholar]
  9. Fehling H. J., Swat W., Laplace C., Kühn R., Rajewsky K., Müller U., von Boehmer H. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science. 1994 Aug 26;265(5176):1234–1237. doi: 10.1126/science.8066463. [DOI] [PubMed] [Google Scholar]
  10. Früh K., Gossen M., Wang K., Bujard H., Peterson P. A., Yang Y. Displacement of housekeeping proteasome subunits by MHC-encoded LMPs: a newly discovered mechanism for modulating the multicatalytic proteinase complex. EMBO J. 1994 Jul 15;13(14):3236–3244. doi: 10.1002/j.1460-2075.1994.tb06625.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glynne R., Powis S. H., Beck S., Kelly A., Kerr L. A., Trowsdale J. A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. Nature. 1991 Sep 26;353(6342):357–360. doi: 10.1038/353357a0. [DOI] [PubMed] [Google Scholar]
  12. Goldberg A. L., Rock K. L. Proteolysis, proteasomes and antigen presentation. Nature. 1992 Jun 4;357(6377):375–379. doi: 10.1038/357375a0. [DOI] [PubMed] [Google Scholar]
  13. Gustincich S., Manfioletti G., Del Sal G., Schneider C., Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991 Sep;11(3):298-300, 302. [PubMed] [Google Scholar]
  14. López-Larrea C., Gonzalez-Roces S., Peña M., Dominguez O., Coto E., Alvarez V., Moreno M., Hernandez O., Burgos-Vargas R., Gorodezky C. Characterization of B27 haplotypes by oligotyping and genomic sequencing in the Mexican Mestizo population with ankylosing spondylitis: juvenile and adult onset. Hum Immunol. 1995 Jul;43(3):174–180. doi: 10.1016/0198-8859(94)00156-k. [DOI] [PubMed] [Google Scholar]
  15. Maksymowych W. P., Suarez-Almazor M., Chou C. T., Russell A. S. Polymorphism in the LMP2 gene influences susceptibility to extraspinal disease in HLA-B27 positive individuals with ankylosing spondylitis. Ann Rheum Dis. 1995 Apr;54(4):321–324. doi: 10.1136/ard.54.4.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maksymowych W. P., Wessler A., Schmitt-Egenolf M., Suarez-Almazor M., Ritzel G., Von Borstel R. C., Pazderka F., Russell A. S. Polymorphism in an HLA linked proteasome gene influences phenotypic expression of disease in HLA-B27 positive individuals. J Rheumatol. 1994 Apr;21(4):665–669. [PubMed] [Google Scholar]
  17. Monaco J. J., McDevitt H. O. H-2-linked low-molecular weight polypeptide antigens assemble into an unusual macromolecular complex. 1984 Jun 28-Jul 4Nature. 309(5971):797–799. doi: 10.1038/309797a0. [DOI] [PubMed] [Google Scholar]
  18. Ploski R., Flatø B., Vinje O., Maksymowych W., Førre O., Thorsby E. Association to HLA-DRB1*08, HLA-DPB1*0301 and homozygosity for an HLA-linked proteasome gene in juvenile ankylosing spondylitis. Hum Immunol. 1995 Oct;44(2):88–96. doi: 10.1016/0198-8859(95)00063-a. [DOI] [PubMed] [Google Scholar]
  19. Ramos-Remus C., Gomez-Vargas A., Guzman-Guzman J. L., Jimenez-Gil F., Gamez-Nava J. I., Gonzalez-Lopez L., Farrera-Gamboa H., Maksymowych W. P., Suarez-Almazor M. E. Frequency of atlantoaxial subluxation and neurologic involvement in patients with ankylosing spondylitis. J Rheumatol. 1995 Nov;22(11):2120–2125. [PubMed] [Google Scholar]
  20. Robinson W. P., van der Linden S. M., Khan M. A., Rentsch H. U., Cats A., Russell A., Thomson G. HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27+ patients. Arthritis Rheum. 1989 Sep;32(9):1135–1141. doi: 10.1002/anr.1780320912. [DOI] [PubMed] [Google Scholar]
  21. Tussey L. G., Rowland-Jones S., Zheng T. S., Androlewicz M. J., Cresswell P., Frelinger J. A., McMichael A. J. Different MHC class I alleles compete for presentation of overlapping viral epitopes. Immunity. 1995 Jul;3(1):65–77. doi: 10.1016/1074-7613(95)90159-0. [DOI] [PubMed] [Google Scholar]
  22. Van Kaer L., Ashton-Rickardt P. G., Eichelberger M., Gaczynska M., Nagashima K., Rock K. L., Goldberg A. L., Doherty P. C., Tonegawa S. Altered peptidase and viral-specific T cell response in LMP2 mutant mice. Immunity. 1994 Oct;1(7):533–541. doi: 10.1016/1074-7613(94)90043-4. [DOI] [PubMed] [Google Scholar]
  23. Vargas-Alarcón G., Garcia A., Bahena S., Melin-Aldana H., Andrade F., Ibañez-de-Kasep G., Alcocer-Varela J., Alarcón-Segovia D., Granados J. HLA-B alleles and complotypes in Mexican patients with seronegative spondyloarthropathies. Ann Rheum Dis. 1994 Nov;53(11):755–758. doi: 10.1136/ard.53.11.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zeidler H., Mau W., Khan M. A. Undifferentiated spondyloarthropathies. Rheum Dis Clin North Am. 1992 Feb;18(1):187–202. [PubMed] [Google Scholar]
  25. van der Linden S. M., Valkenburg H. A., de Jongh B. M., Cats A. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum. 1984 Mar;27(3):241–249. doi: 10.1002/art.1780270301. [DOI] [PubMed] [Google Scholar]
  26. van der Linden S., Valkenburg H. A., Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984 Apr;27(4):361–368. doi: 10.1002/art.1780270401. [DOI] [PubMed] [Google Scholar]

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