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PubMed1975

Information processing immunogenetic analysis. IV. Information amount and predictive power of different immunogenetic models.

Principles of information theory are imposed on immunogenetic information processing, whereby the 'information amount', simplicity, 'redundancy' and 'predicatability' of different encodings, models, theories or mappings can be objectively compared. As an example, the experimental observables emanating from the Rh system at its 10 reagent-8 haplotype level is shown to obtain an information amount of 140,120 and 78 bits when interpreted (encoded according to a simple-complex, complex-simple and complex-complex theory, model or program, respectively. The 'predictive' or 'accomodating' power of the simple-complex and complex-simple theories is shown to be 134, respectively 366 bits for a given set of experimental observables emanating from a S3 universe.

Computers↗

PubMed1978

Lipoprotein immunogenetics and atherosclerosis.

The discovery of the first human lipoprotein polymorphism by Allison and Blumberg [Lancet i:634-637, 1961] and the availability of alloimmune sera stimulated us to begin immunogenetic studies on swine in search of lipoprotein diversity and its relationship to biological functions. We found considerable lipoprotein polymorphism, complexity, and heterogeneity in this species. These results and the correlation between immunogenetically defined lipoprotein type and arterial lipidosis in swine, fed a high fat diet, are discussed. Immunogenetic studies of lipoproteins, initiated more recently in rhesus monkeys, will be reviewed also. Preliminary data show similarities between these two species with regard to polymorphism, complexity, phenotypic expression of lipoprotein genes and, most importantly, their serological relationship to human lipoproteins. We also note immunogenetic studies on lipoproteins done by other investigators, or in other species. Brief remarks on implications of the lipoproteins in atherosclerosis, their general classification, immunological properties, and immunological methods used in their study precede the immunogenetic presentation.

Animals↗

PubMedDate not supplied

Towards a unified theory for immunogenetic systems. Some selected properties of ABC- and AB-D reaction patterns generated by S3 and T3 universes.

The principles of a radically new unified theory and a unified but fundamentally theory-invariant classification system are described and exemplified for immunogenetic systems. The classification system permits a differentiation of immunogenetic systems into 15 qualitatively distinct classes with quantitative subsets when tested against two reagents. It can easily be expanded into a n-reagent taxonomy. The theory logically explains a set of selected and previously more or less "unexplainable" properties and their (even more unexplainable and probably previously unnoticed) associations in two main classes of immunogenetic systems, the ABC- and AB-D systems. The associated properties discussed are the presence (+) or absence (-) of: 1. antithetical alleles; 2. dosage effects; 3. inherited "strong" and "weak" antigens; 4. "silent" or "amorphous" genes. In ABC- systems, properties 1 and 2 are present while 3 and 4 are absent or extremely rare (i.e. 1+2+3-4-). In AB-D systems, properties 1 and 2 are absent while 3 and 4 are present (i.e. 1-2-3+4+). Through the design of hypothetical immunogenetic universes (HIU), these property associations are shown to be produced by the contemporary (simple-complex) framework-dependent transformations of experimental observables/matrix facts and not by any corresponding associated properties present in the input HIU in themselves.

ABO Blood-Group System↗

PubMed1991

Subacute cutaneous lupus erythematosus-immunogenetic associations.

Thirty-two patients who fulfilled criteria for subacute cutaneous lupus erythematosus (SCLE) were examined for their immunogenetic associations. Our results confirm the previously reported association of HLA-DR3 (15/31 48% P less than 0.01) and also demonstrate an increase in HLA-DR2 (14/31, 45%, P = less than 0.05). These findings indicate there are two distinct immunogenetic (HLA) populations of Ro(SS-A) antibody-positive SCLE patients. The increased frequency of HLA-DR2 and DR3 appears to be associated with expression of the Ro(SS-A) antibody, since no HLA associations were seen in Ro(SS-A)-negative SCLE patients when compared with normal population controls. Furthermore, these data indicate that the distinctive cutaneous lesions of SCLE are not associated with one specific HLA allele, as previously suspected. These findings contrast with the relatively homogeneous immunogenetic background seen in other lupus erythematosus subsets with a high frequency of Ro(SS-A) antibody, i.e., neonatal lupus erythematosus and Sjögren's syndrome/lupus erythematosus overlap (increased frequency of HLA-DR3, DQw2 and DRW52).

Adult↗

PubMed1989

Immunogenetics of experimental autoimmune myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune neuromuscular disease manifested by muscle weakness and fatiguability. The primary pathology in MG is antibody and complement-mediated destruction of muscle acetylcholine receptor (AChR). Like other autoimmune diseases, MG is associated with certain HLA antigens, particularly HLA-B8 and DR3 in Caucasians. Also, certain GM antigens and complotypes are associated with MG. Therefore, it is crucial to study the immunogenetic aspect of MG in animal models to evaluate disease etiopathogenesis and eventual strategy for specific therapy. In the introduction of this review article, I focus on the association of HLA and GM antigens in MG and emphasize the mouse model of experimental autoimmune myasthenia gravis (EAMG) as an ideal model to study the immunogenetic aspect of MG. The following sections deal with the role of (1) major histocompatibility complex (MHC), (2) immune response gene, (3) the IA molecule, (4) the Igl locus, (5) the complement genes, and (6) non-MHC genes on EAMG pathogenesis. The review concludes with future immunogenetic analysis and eventual strategy for specific therapy from an immunogeneticist's point of view.

Animals↗

PubMed1992

Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations.

OBJECTIVE: The inflammatory myopathies are characterized by distinctive autoantibodies that are associated with certain clinical features and immunogenetic patterns. Anti-PM-Scl is one such antibody and is found in pure myositis, myositis in overlap, and systemic sclerosis (SSc). Our purpose was to describe the clinical and immunogenetic associations of the anti-PM-Scl antibody. METHODS: Serum samples from 617 patients with various connective tissue diseases were screened for anti-PM-Scl antibody by indirect immunofluorescence and Ouchterlony double immunodiffusion. Patients with anti-PM-Scl were serologically typed for HLA-DR and DQ, and the genes encoding DQ alpha and DQ beta were characterized by hybridization of sequence-specific oligonucleotide to amplified genomic DNA. RESULTS: Twenty-three patients (4%) had serum anti-PM-Scl. Sixteen had either pure myositis or myositis in overlap, 6 had SSc alone, and 1 had SSc and rheumatoid arthritis. Twenty of the antibody-positive patients had serologic HLA typing performed; 15 (75%) were HLA-DR3 positive, and 17 (85%) expressed the DQw2 allele. None of the 5 DR3 negative patients shared a unique DR or DQ antigen with the DR3 positive patients, and further DNA analysis of 10 patients (4 of whom were DR3 negative) did not reveal any unique DQ alleles. CONCLUSION: Anti-PM-Scl identifies a subset of patients with myositis, SSc, or an overlap of the two disorders, and this antibody has a strong but not exclusive immunogenetic association with the HLA-DR3 antigen.

Adolescent↗

PubMed1976

Codominant inheritance in immunogenetic (IR-gene) systems.

Immunogenetic (IR-gene) systems consist of animals showing different quantitative antibody responses when immunized with similar doses of a given antigen. Strains of animals giving high and low antibody titres are described as high and low responders, respectively. The degree of dominance in F1 hybrid strains, obtained from a cross between high and low responder parents, can readily be calculated using the dominance index formula, which takes the value of +1 for complete dominance, -1 for complete recessivity and the value of zero for no dominance. In reviewing 1527 F1 animals, obtained from ninety-one immunogenetic systems, the degree of diminance (d) was found to be: +0-0076 +/- 0-1053 (mean +/- s.e.), which is close to a value of zero and this is consistent with codominant inheritance. It is suggested that in immunogenetic systems, both alleles are expressed as codominant genes.

Animals↗

PubMed1992

[Immunogenetic and molecular genetic studies on ocular diseases].

The immunogenetic mechanisms of various ocular diseases were investigated utilizing recently developed molecular biological and molecular genetic techniques. It was revealed that HLA-B 51 was closely associated with Behçet's disease. Investigation of genetic polymorphism of TNF-beta (tumor necrosis factor-beta) showed that 95% of Behçet's disease patients had the 10.5 kbp Nco I fragment. It was therefore concluded that the gene of susceptibility to Behçet's disease is located between HLA-B and TNF-beta loci on the short arm of chromosome 6. Similar studies of HLA-DNA typing in Harada's disease frequently seen in Japan showed that frequencies of HLA-DRB1 * 0405, HLA-DQA1 * 0301 and HLA-DQB1 * 0401 were significantly increased in patients compared with normal controls. These data suggested that those who have serine at position 57 of HLA-DR, glutamic acid at position 70 and aspertic acid at position 71 of HLA-DQ respond to certain unknown agents significantly more than those without them, thus leading to the development of Harada's disease. The same HLA association was observed between Harada's disease and sympathetic ophthalmia, and the immunogenetic mechanism was thought to be similar in both diseases. Recent immunogenetic and molecular genetic investigations on various ocular diseases have shed new light not only on the genetic individual susceptibility and biased racial differences, but also on the diagnosis of the ocular diseases, reclassification of disease entities according to HLA associations, and judgement of disease prognosis. Further progress of molecular medicine may make it possible to treat various intractable ocular diseases by gene therapy in the near future.

Amino Acid Sequence↗

PubMed1990

[A clinico-immunogenetic method of prognosis in retrobulbar neuritis as an initial manifestation of multiple sclerosis].

Examination of 166 patients with optic neuritis revealed that 65 of them developed multiple sclerosis (MS) at different times after optic neuritis. The observation period was 9.4 years on the average. Using the clinical, laboratory, immunogenetic methods the clinico-immunogenetic heterogeneity of optic neuritis was discovered, the highly informative specific clinical signs and immunogenetic markers suitable as criteria for predicting different variants of optic neuritis outcomes were defined. Using a heterogeneous successive procedure a method of individual ++pre-nosological prediction of MS in persons with a history of optic neuritis was devised.

Adolescent↗

PubMed1976

The use of early embryo aggregation derived mouse chimaeras. III. A tool of immunogenetics.

Early embryo aggregation derived chimaeras have proven a valuable tool to biologists concerned with various aspects of mammalian development. The use of this model is discussed here in respect of its application to the field of immunogenetics and also to possible future exploitation. Chimaeras have already provided information concerning various areas of immunogenetics ranging from tolerance, control of antibody response, allotype expression, gene transfer and its possible influence upon the immune response. These are reviewed here.

Aging↗

PubMed1976

Immunogenetic factors in aetiology of pre-eclampsia/eclampsia (gestosis).

The evidence that genetic and immunogenetic influences operate in the causation of pre-eclampsia/eclampsia (gestosis) is reviewed. The problems of definitive diagnosis are discussed along with the possibility of a multifactorial aetiology. The difficulties of differentiating trigger and effector mechanisms are also considered. It is concluded that there is evidence for a predisposition, probably genetic, operating in some cases, an immunogenetic mechanism in others, and chromosomal factors in a small group.

Aneuploidy↗

PubMed1992

Immunogenetic and hormonal study of cryptorchidism.

Ninety-four cryptorchids, 50 monolateral and 44 bilateral, aged from 2-9.4 yr (mean, 5.1 +/- 0.5 yr), were studied for the hormonal and immunogenetic profile. Pituitary-gonadal function was studied by evaluation of basal and peak GnRH-stimulated serum FSH and LH. In 83 cases, the serum testosterone (T) level was measured before and after CG treatment. No significant differences, between patients and age-matched controls, were found in either FSH or LH levels, whether under basal conditions or after GHRH stimulation. The mean basal serum T level was similar in mono and bilateral cryptorchids and in controls but, on the 15th day after treatment, it was significantly lower in the bilateral cryptorchids (P less than 0.05). CG administration led to testicular descent in 42 patients (23 with monolateral and 19 with bilateral cryptorchidism) and failed in 41 (21 with monolateral and 20 with bilateral cryptorchidism), independently of T increase. Immunogenetic investigation demonstrated that HLA-A11 and A23 were significantly overrepresented in the whole group of cryptorchids in comparison with the controls (P = 0.004 and P = 0.0123, respectively). HLA-A11 was more common in the bilateral form (P less than 0.05), whereas HLA-A29 was more frequent in the monolateral one (P less than 0.05). Forty percent of the bilateral cryptorchids with unsuccessful treatment had the HLA-A11 allele (P less than 0.01) and 70% the HLA-DR5.

Child↗

PubMed1991

Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy.

We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.

Aged↗

PubMed1978

Morphological reaction in transplanted small intestines using immunogenetically defined rat strain combinations.

From the inbred rat stains F344, LEW and Brown-Norway (BN), the following combinations were formed: syngeneic (LEW--LEW), weakly allogeneic (F344--LEW) and strongly allogeneic (BN--LEW). A small intestine segment was transplanted using the by-pass technique; after 10 days the graft was removed and histologically investigated. The strongest rejection was found in the lymphatic tissue and the epithelium of the small intestinal transplant. The immunogenetical difference is significant for the survival of the graft: the greater the immunogenetical difference between donor and host, the more severe the morphologically demonstrable rejection reaction.

Animals↗

PubMed1988

Non-responsiveness to hepatitis-B vaccination: revaccination and immunogenetic typing.

The variation in immune responses to standard inoculation of the hepatitis-B virus vaccine suggest that host factors influence response in ways that are not presently understood. We studied 25 low/nonresponding health care workers (anti-HBs titer less than 50 IU/l) after the third inoculation of an experimental hepatitis-B vaccine to determine their immune status (through lymphocyte phenotypes) and HLA type. After application of a fourth inoculation, the seroconverting subjects showed only low anti-HBs levels; three male subjects remained anti-HBs negative. Twelve months after the fourth inoculation only 9 of 25 subjects (36%) maintained anti-HBs titer greater than 10 IU/l. Almost all subjects had normal B-cell and CD-4 and CD-8 counts and ratios. Relative to other European populations HLA-A-10 (P less than 0.05), B-12 (P less than 0.025), CW-5 (P less than 0.05), DR-3 (P less than 0.025), and DR-5 (P less than 0.025) were increased, whereas DR-2 (P less than 0.05) was decreased. However, after correction of the P-values for the number of HLA antigens determined, these differences were no longer significant. Furthermore, these HLA types were not the same as those reported in other studies (except for DR-3). We suggest that larger sample sizes or even not yet available immunogenetic markers will be required to prove an "immunogenetic background" in low/nonresponders, if it exists.

Adolescent↗

PubMed1987

Immunogenetic factors as determinants of asbestosis.

To evaluate the possible role of immunogenetic factors as predisposing determinants of the development of asbestosis in exposed workers, we obtained 53 phenotypes of the human leucocyte antigen (HLA)-A, B, C, and DR antigens in 72 long-term workers of the mines and mills of Quebec and in a reference population of 150 residents. Among the asbestos workers, 32 did not have any abnormality and 40 had asbestosis. The 2 groups did not differ in term of age, exposure, or cigarette smoking habits. In agreement with previous reports, we found no significant change in frequency of the HLA-A, B, or C phenotypes. Furthermore, we did not find any significant change in the frequency of 10 phenotypes of the HLA-DR loci. We conclude that immunogenetic factors are not major predisposing determinants of asbestosis.

Aged↗

PubMed1986

Primary Sjögren's syndrome in men. Clinical, serologic, and immunogenetic features.

Although primary Sjögren's syndrome is a common rheumatic disorder in women, it is not well recognized in men. This study represents the first report of the clinical, serologic, and immunogenetic features of a group of 36 men with primary Sjögren's syndrome, which are contrasted with those of a group of 69 women with primary Sjögren's syndrome. The majority of male patients had extraglandular involvement including articular (78 percent), neurologic (39 percent), inflammatory vascular (25 percent), and lymphoproliferative disorders (17 percent). Although men were at the same risk for the development of extraglandular complications, there were significant serologic and immunogenetic differences. In sharp contrast to women with Sjögren's syndrome, men with Sjögren's syndrome were seronegative with respect to the presence of serum rheumatoid factor (p = 0.008) and antibodies to Ro(SS-A) (p = 0.016). The supertypic specificity, MT2 (DRw52), as in women, was strongly associated with primary Sjögren's syndrome in men when compared with race-matched control subjects (p = 0.0015). In men, however, the frequency of HLA-B8 and HLA-DR3, the most common DR locus specificity observed in women, was not statistically different from that observed in the normal control group.

Adult↗

PubMed1991

An immunogenetic view of delayed type hypersensitivity.

This review, the third in the series on cellular immune reactivity to tubercle bacilli in the centenary year of Koch's classical paper describing this phenomenon and its possible implications, represents an immunogenetic point of view. In fact this will be quite a broad point of view by an immunogeneticist who is not hampered by specific knowledge on therapy or prevention of tuberculosis. In this respect I probably do not differ very much from Robert Koch 100 years ago! An important difference, however, is that we think we now understand a great deal of the cellular and molecular basis of the immunological phenomena observed by Koch. Immunogenetics has contributed considerably to our current understanding and I will try to review that contribution here. Because thus far my main research interest has been in another mycobacterium, namely Mycobacterium leprae, I will use M. leprae and leprosy as an example to illustrate some ideas. The message of this review is that there is a reason for optimism: the knowledge recently gained by cellular and molecular immunologists as well as immunogeneticists has straightforward implications for the rational development of subunit vaccines and immunotherapeutic strategies.

HLA Antigens↗