Association of complement allotype C4B2 with anterior uveitis

doi:10.1016/0198-8859(88)90032-8

Human Immunology

Volume 21, Issue 4, April 1988, Pages 233-237

https://doi.org/10.1016/0198-8859(88)90032-8 Get rights and content

Abstract

We have studied allotypes of the fourth component of complement (C4) in 44 patients with inflammatory eye disease in order to define genetic susceptibility factors further. Twenty-six patients had uveitis (18 had anterior uveitis) and 18 patients had retinal vasculitis. There was an increased incidence of the C4B2 allotype in patients with anterior uveitis (p_c < 0.002), especially in HLA B27 positive males. In contrast, there was no increased incidence of specific allotypes in patients with posterior uveitis or retinal vasculitis. This genetic association may form part of a disease susceptibility supratype in patients with anterior uveitis.

References (19)

D.A. Brewerton et al.
Acute anterior uveitis and HL-A27
Lancet
(1973)
D. Wakefield et al.
HLA antigens in uveitis
Hum Immunol
(1983)
M. Reynard et al.
Histocompatibility antigens in sympathetic ophthalmia
Am J Ophthalmol
(1983)
S. Ohno et al.
Specific histocompatability antigens associated with Behcet's disease
Am J Ophthalmol
(1975)
R.B. Nussenblatt et al.
Birdshot retinochoroidopathy associated with HLA A29 antigen and immunoresponsiveness to retinal S antigen
Am J Ophthalmol
(1982)
D. Wakefield et al.
HLA DR4 associated with retinal vasculitis
Hum Immunol
(1985)
D.A. Brewerton et al.
The alpha 1-anti trypsin phenotype MZ in acute anterior uveitis
Lancet
(1978)
C.W. Nerl et al.
Complement C4 allotypes in Alzheimer's disease
Lancet
(1982)
R. Schroder et al.
Multiple sclerosis: Immunogenetic analysis of sib pair double case families. II. Studies on the association of multiple sclerosis with C2, C4, Bf, C3, C6, and GLO polymorphisms
Immunobiology
(1983)

There are more references available in the full text version of this article.

Cited by (14)

Therapeutic targeting of the complement system in ocular disease
2023, Drug Discovery Today
The complement system is involved in the pathogenesis of several ocular diseases, providing a rationale for the investigation of complement-targeting therapeutics for these conditions. Dry age-related macular degeneration, as characterised by geographic atrophy (GA), is currently the most active area of research for complement-targeting therapeutics, with a complement C3 inhibitor approved in the United States earlier this year marking the first approved therapy for GA. This review discusses the role of complement in ocular disease, provides an overview of the complement-targeting agents currently under development for ocular conditions, and reflects on the lessons that can be learned from the preclinical investigations and clinical trials conducted in this field to date.
Distribution of complement anaphylatoxin receptors and membrane-bound regulators in normal human retina
2006, Experimental Eye Research
Citation Excerpt :
Differences in staining between peripheral and macular sections were described above for the C3aR. The complement system, first described over 100 years ago, has received renewed attention with an increasing body of evidence implicating it in a number of human diseases of importance, including those affecting the eye (Gerl et al., 2002; Hageman et al., 2001, 2005; Johnson et al., 2000, 2001b; Klein et al., 2005; Mondino and Sumner, 1986; Mondino et al., 1988, 1990; Mullins et al., 2000, 2001; Wakefield et al., 1988). Activation of the complement system through any of the three initiation pathways (classical, lectin, or alternative) results in a cascade of enzymatic cleavages leading to the production of the anaphylatoxins C3a and C5a, the opsonins C3b and C4b, and the membrane attack complex.
To characterize the distribution of membrane-bound components of the complement system in normal human retina, eyes from eight human donors with no history of ocular disease, ranging in age from 47 to 85 years were examined using immunohistochemistry to localize the C3a receptor (C3aR), C5a receptor (C5aR), CD46, CD55, and CD59 in cryosections prepared from donor posterior segments. The C3aR was identified in the nerve fiber layer in a sawtooth-patterned band. Vimentin, used as a Müller cell marker, produced a similar staining pattern. The C5aR was detected on specific rounded structures in the inner plexiform layer and occasionally in the nerve fiber layer. CD46 produced markedly specific staining of the basolateral surface of the retinal pigment epithelium. CD55 was localized to the nerve fiber layer. Staining for these proteins was consistent across all eyes studied. CD59 was expressed throughout the nerve fiber layer and labeled vessels that extended through the ganglion cell, inner plexiform, and inner nuclear layers, but this pattern was only confirmable in a single subject. Complement anaphylatoxin receptors and regulatory proteins are localized in different but internally consistent patterns in normal adult human retina, independent of the age of the donor. C3aR and C5aR localization only in the inner retina contrasts with previously reported findings in the central nervous system of wide spread diffuse staining. The complement regulators CD55 and CD59 were found primarily on the inner retina, while CD46 was present exclusively in a polarized fashion on the RPE.
Genetic and immunologic studies of patients on procainamide
1998, Human Immunology
Forty (40) patients with cardiac arrhythmias receiving procainamide (PA) therapy and 24 patients who were receiving other drugs for their cardiac disorders were investigated for class II HLA phenotypes and their DRB1∗04 and DQB1∗03 subtypes. Other genetic marker evaluations in the PA patients included: 1) class III MHC C4A and C4B null alleles of complement; and, 2) acetylation phenotype.
Twenty (20) of the PA patients were also tested for the ability of their stimulated cells to secrete Interleukin-1 (IL-1β) and tumor necrosis factor (TNFα). We also examined the spontaneous production of these cytokines by peripheral blood leukocytes (PBL) from patients who were receiving chronic PA treatment.
The results revealed no association of acetylation phenotypes with the class II HLA phenotypes nor class III MHC C4 allotypes in these patients. The results did show a significant increase in class III C4 complement allotypes in the PA patients when compared to the controls. The results also showed a significant increase in autoantibodies and DQw3 phenotypes in the PA patient group when compared to control populations. Results of spontaneous IL-1 and TNF production suggested there may be an association of select class II HLA phenotypes in some patients and this may be relevant to host responsiveness to PA treatment.
Acute anterior uveitis and HLA-B27
1991, Survey of Ophthalmology
Acute anterior uveitis is a common ocular disease characterized by inflammation of the iris and ciliary body. In the majority of patients presenting with an acute attack of anterior uveitis, the only clues to the pathogenesis of this disease are its close association with the genetic marker HLA-B27 and the likely triggering role of a variety of gram negative bacteria. HLA-B27 acute anterior uveitis appears to be a distinct clinical entity frequently associated with the seronegative arthropathies, such as ankylosing spondylitis and Reiter's syndrome. Recent advances in our understanding of the structure and function of class I HLA molecules have revealed their fundamental function in antigen presentation and this has led to a reevaluation of their role in disease predisposition.
Associations between restriction fragment length polymorphisms detected with a probe for human C4 and allotype of C4B5 allele
1990, Human Immunology
We studied the fourth component of human complement (C4) allotypes in 58 Japanese individuals. The technique of Southern, with C4 and 21-OH cDNA probes, was used to examine the genomic DNA of 45 individuals typed for C4 by protein electrophoresis. Novel HindIII C4 10- and 5-kb and EcoRI C4 13-Kb restriction fragments were identified in each of nine Japanese individuals. The novel fragments were different from the previously described C4B long (HindIII 31-kb, TaqI 6-kb, BamHI 4.3-kb, and EcoRI 12-kb) and C4B short (HindIII 25-kb, TaqI 5.4-kb, BamHI 3.5-kb, and EcoRI 15-kb) fragments. All novel HindIII- and EcoRI-positive individuals carried C4B5, BfS, and HLA-Bw54. Therefore, the fragments were characteristic for the C4B5 allele. The C4 region was analyzed to determine the restriction sites by single and double digests of uncloned genomic DNA with several restriction endonucleases. It is speculated that an insertion gene lies between the 3' end of the 21-OH and the 5' end of the C4B genes.
Complement component C4 regulates the development of experimental autoimmune uveitis through a T cell-intrinsic mechanism
2017, Frontiers in Immunology

View all citing articles on Scopus

View full text

Association of complement allotype C4B2 with anterior uveitis

Abstract

Lancet

Hum Immunol

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Hum Immunol

Lancet

Lancet

Immunobiology