Hla–Dr4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragéeaes

Grosse‐Wilde, H.; Genth, E.; ühl, Audrey Grevesm; Vögeler, U.; Zarnowski, H; Mierau, Rudolf; Doxiadis, G.; Doxiadis, Ilias; Maas, D.

doi:10.1002/art.1780300806

Cited by 7 publications

(2 citation statements)

References 29 publications

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“…Although unusual, nonimmune neurological functions can be proposed, the implication of immune system genes (e.g., HLA-haplotype association and SH linkage) suggests an immunopathology in both the narcoleptic canines and humans. This condition would be consistent with the observed relationships in humans between HLA-associated autoimmune diseases and immunoglobulin heavy-chain polymorphisms (22)(23)(24)(25)(26)(27)(28)(29)(30). Involvement of immune mechanisms in the pathophysiology of narcolepsy and, by logical extension, in control of rapid-eye-movement sleep has been suggested previously (3,(6)(7)(8)(9).…”

Section: Methodssupporting

confidence: 86%

Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment.

Mignot

Wang

Rattazzi

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Identification of genes determining narcolepsy susceptibility is important not only for understanding that disorder but also for possible clues to general sleep-control mechanisms. Studies in humans reveal at least one such gene related to the major histocompatibility complex and in dog anas-yet-unmapped single, autosomal recessive gene canarc-1. Gene markers for canarc-l were therefore sought by DNA restriction fragment length polymorphisms in our colony of narcoleptic dogs. A human ,I-switch immunoglobulin probe and the enzyme Hae III identified a gene cosegregating with canarc-l in backcrossed animals (logarithm of odds scores: m = 24, Z max = 7.2 at 0 = 0%). canarc-1 was also shown not to be tightly linked with the dog major histocompatibility complex (m = 40, Z < -2 at 0 < 4.8%). These results represent the mapping of a non-major histocompatibility complex narcolepsy gene and strongly suggest involvement of the immune system in the pathophysiology of that disease. Human narcolepsy is a sleep disorder characterized by excess daytime sleepiness, disturbed nocturnal sleep, and pathological manifestations of rapid eye movement sleep, including sleeponset rapid eye movement periods, cataplexy, sleep paralysis, and hypnagogic hallucinations. The cause and the pathogenesis of narcolepsy are unclear but involve both genetic and environmental factors (1, 2). One genetic factor appears in association with the major histocompatibility complex (MHC) haplotype HLA-DRw1S (DR2), Dw2, DQw6 (DQw1), which is present in 32.8% of Caucasian and 7.7% of Asian normal controls, respectively, compared with 90-95% of Caucasian and 100%o of Asian narcoleptic patients (1,(3)(4)(5).This finding has led to the hypothesis that narcolepsy may be an autoimmune disorder or that a gene encoding an essential protein for sleep control may be located within the MHC complex. Studies to date, however, have not found evidence for or against these hypotheses. None of the general tests of immunopathology described in other autoimmune disorders (peripheral blood erythrocyte sedimentation rate, C-reactive protein, complement, immunoglobulins and lymphocyte subpopulations, cerebrospinal fluid oligoclonal bands) have been found abnormal in narcoleptic patients (6-9), DNA studies have thus far failed to reveal differences between the DRw15 and DQw6 genes of narcoleptics and those of normals (10, 11), and numerous nonimmunological genes cloned within the MHC region do not seem related to sleep.The paucity of multicase families has hindered further genetic studies. Nevertheless, sufficient patients without the DRw15 (DR2) haplotype, as well as multiplex families with disease not linked to HLA, have been reported (1, 2), strongly suggesting the existence of human non-MHC nar- MATERIALS AND METHODSBackcrosses and Diagnosis of Narcolepsy. Canine narcolepsy is an autosomal recessive disorder with full penetrance. Cataplexy can be observed spontaneously or after induction, by using the food-elicited cataplexy test (12) in all adult animals born from nar...

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Section: Methodssupporting

confidence: 86%

Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment.

Mignot

Wang

Rattazzi

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…The third type of association is described as interactive, in which independent HLA and Gm associations cannot be defined alone, but they produce an increased risk for disease together. Interactive HLA and Gm effects have also been demonstrated in diseases such as chronic active hepatitis, and in the expression of specific immune responsiveness (or unresponsiveness) to immunogens in healthy individuals (1 3,14).…”

Section: Van Kerckhove and Glassmentioning

confidence: 99%

The immunoglobulin supergene family and the polygenic nature of inherited predisposition to rheumatic disease

Kerckhove

Glass

1987

Arthritis & Rheumatism

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Gm allotype system and autoimmune diseases

Abu‐Shakra

Shoenfeld

1989

Immunol Res

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Hla–Dr4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragéeaes

Cited by 7 publications

References 29 publications

Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment.

Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment.

The immunoglobulin supergene family and the polygenic nature of inherited predisposition to rheumatic disease

Gm allotype system and autoimmune diseases

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