HLA and Disease Associations

The human leukocyte antigen (HLA) or tissue types are the products of a rapidly developing field of knowledge within the last 20 years. In the early stages of the research many investigators suspected the existence of a complex series of transplantation antigens, but it was widely believed that these antigens would not be well-defined even in this century. Yet in the last two decades as many as 124 different HLA antigens determined by at least 7 very closely linked genes located on the short arm of chromosome 6 have been identified and subsequently agreed upon by an international nomenclature committee. 1 Extensive international collaboration fueled by the potential clinical application of these antigens to clinical transplantation has advanced the field rapidly. There were nine inter national histocompatibility workshops held during this period. Although iden tification of HLA antigens was of primary clinical importance in transplantation 2 and of great basic interest in human genetics and anthropology, a rather un expected bonus has been the determination that HLA antigens are associated with disease susceptibility to a greater extent than any other known genetic marker in man. In the past, many genetic polymorphisms have been suspected to be associated with diseases. The most extensively studied markers are blood groups, enzymes, and serum proteins. A comprehensive account of published studies, totalling approximately 1,000, of these markers is available in a book by Mourant et al.

1 HLA Nomenclature.- 2 The HLA Complex.- History.- The Genes of the HLA Complex.- Inheritance of HLA.- Frequencies of HLA Antigens.- Racial Variations in Antigen Frequencies.- Cross-Reactivity.- Linkage Disequilibrium.- Typing Methodology.- 3 The Data and Statistical Analysis.- The Data.- Population Data Analysis.- Family Data Analysis.- Diagnostic Value of HLA Typing.- Interpretation of the Data and the Analysis.- 4 Mechanisms of HLA and Disease Associations.- General Background.- Mechanisms.- 5 Overview.- Summary of the Most Significant Associations.- HLA Antigens Associated with Diseases.- 6 Rheumatology and Joint Diseases.- Brachymetacarpia.- Congenital Dislocation of Hip.- Spina Bifida.- Idiopathic Scoliosis.- Ossification of Posterior Longitudinal Ligament of the Cervical Vertebrae.- Dactylitis ("Sausage-Like" Toes).- Hydroxyapatite Rheumatism (Calcific Periarthritis).- Low Back Pain.- Chondrocalcinosis.- Hereditary Chondrocalcinosis.- Perthes' Disease.- Paget's Disease.- Frozen Shoulder.- Arthritis (Unspecified).- Rheumatoid Arthritis.- Juvenile Rheumatoid Arthritis.- Malignant Rheumatoid Arthritis.- Seronegative Pauciarticular Arthritis.- Seronegative Peripheral Arthritis.- Seronegative Chronic Polyarthritis.- Gonococcal Arthritis.- Psoriatic Arthropathy (Unspecified).- Psoriatic Arthropathy (Central).- Psoriatic Arthropathy (Peripheral).- Psoriatic Arthropathy (Peripheral and Sacroiliitis).- Post-Yersinia Arthritis.- Postgonorrhoic Arthritis.- Postshigellosis Arthritis.- Postmeningococcal Arthritis.- Postrubella Vaccination Arthropathy.- Post-Salmonella Arthritis.- Septic Arthritis Due to Klebsiella.- Reactive Arthritis After Campylobacter jejuni Enteritis.- Reactive Arthritis After Mycoplasma pneumoniae Infection.- Sexually Acquired Reactive Arthritis.- Pseudopolyarthritis of the Spine.- Ankylosing Spondylitis.- Ankylosing Spondylitis in Inflammatory Bowel Disease.- Seronegative "Spondylitic Variant" Syndrome.- Vertebral Ankylosing Hyperostosis (Forestier's Disease).- Sacroiliitis.- Polyarthrosis of Hands.- Mechanical Disorders of the Spine.- Osteoarthritis.- Osteitis Condensans Ilii.- Juvenile Dermatomyositis.- Caplan's Syndrome.- Neurogenic Paraosteoarthropathy.- Spondylarthritis in Chronic Brucellosis.- Amyloidosis in Rheumatoid Arthritis.- Gout.- Reiter's Disease.- 7 Dermatology.- Psoriasis Vulgaris.- Pustular Psoriasis.- Guttate Psoriasis.- Erythrodermic Psoriasis.- Persistent Palmoplanter Pustulosis (Pustulosis Palmaris et Plantaris).- Flexural Psoriasis (Psoriasis Inversus, Intertriginous Psoriasis).- Pemphigus Vulgaris.- Pemphigus Foliaceus.- Bullous Pemphigoid.- Benign Mucosal Pemphigoid (Cicatrical Pemphigoid, Ocular Pemphigus).- Benign Familial Pemphigus (Hailey-Hailey's Disease).- Subacute Cutaneous Lupus Erythematosus.- Discoid Lupus Erythematosus.- Atopic Dermatitis.- Atopy (Unspecified, Includes Eczema).- Dermatitis Herpetiformis.- Psoriasiform Napkin Dermatitis.- Seborrheic Dermatitis.- Epidermolysis Bullosa.- Vitiligo.- Urticaria.- Acne Conglobata.- Alopecia Areata.- Keloids and Hypertrophic Scars.- Liehen Planus.- Liehen Sclerosus et Atrophicus.- Pityriasis Rubra Pilaris.- Generalized Granuloma Annulare.- Localized Granuloma Annulare.- Kawasaki's Disease (Mucocutaneous Lymph Node Syndrome).- Behçet's Disease.- Xeroderma Pigmentosum.- Desquamative Erythroderma.- Hutchinson-Guilford Progeria Syndrome.- Werner's Syndrome.- Keratoacanthoma.- Felty's Syndrome.- Goltz-Gorlin Syndrome (Dermal Hypoplasia).- Geographic Tongue.- Erythema Multiforme.- 8 Neurology.- Multiple Sclerosis.- Myasthenia Gravis.- Spinocerebellar Ataxia.- Friedreich's Ataxia.- Muscular Dystrophy.- Myotonic Dystrophy.- Neurolathyrism.- Chronic Relapsing Idiopathic Inflammatory Polyneuropathy (Guillain-Barré Type).- Guillain-Barré Syndrome.- Bell's Palsy (Idiopathic Facial Palsy).- Amyotrophic Lateral Sclerosis.- Migraine.- Cluster Headache.- Infantile Spasms (West's Syndrome).- Epilepsy.- Lennox-Gastaut Syndrome.- Paraplegia and/or