Sex distribution, age of onset and HLA profiles in two types of multiple sclerosis

Lambalgen, R. Van; Sanders, E. A. C. M.; D’Amaro, J.

doi:10.1016/0022-510x(86)90138-3

Cited by 77 publications

(7 citation statements)

References 19 publications

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“…The frequency of DQ antigen was normal in our population but higher in a selected subgroup of patients (with normal IgG Index, Table IV). As far as the correlation between HLA and clinical parameters is concerned, we stress the overrepresentation of B7, B8 and DR3 antigens in patients with progressive course, confirming previous studies [11,12,21,22,31]. These antigens are frequently found in autoimmune disease [9], a finding that supports the role of a disorder ofimmunoregulation in the pathogenesis of MS. Gm and -DR loci are probably involved in the modulation of the intrathecal humoral immune response [25,26], but studies on correlation between HLA antigens and CSF parameters have provided no clear evidence for the influence of HLA genes on immunological parameters in MS. Stendahl-Brodin [28], Dejaegher [5] and Rumbach [22] found an increase of B7 and/or DR2 antigen frequency in patients with pathological CSF, but statistically significant differences emerged only in the last study.…”

Section: Discussionsupporting

confidence: 82%

HLA antigens in Italian multiple sclerosis patients

Mantia

Illeni²,

Milanese

et al. 1991

Ital J Neuro Sci

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We analyzed HLA-A, -C, -B, -DR and -DQ specificities in 104 Italian multiple sclerosis patients and in 905 healthy controls. The frequencies of HLA-A23, A26, Cw4, DR3 and, especially DR5 antigens were significantly higher in multiple sclerosis patients than in controls. Patients with progressive course were characterized by high frequencies of B7, B8 and DR3 antigens: Cw1 and DRw11 shows a negative correlation with the extent of intrathecal IgG production. These data confirm that the HLA system may influence the clinical expression and the immune responses to the disease.

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Section: Discussionsupporting

confidence: 82%

HLA antigens in Italian multiple sclerosis patients

Mantia

Illeni²,

Milanese

et al. 1991

Ital J Neuro Sci

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“…In Arabian (38) as well as in Sardinian (39) MS patients an association with the DR4 antigen has been found. A weak association with the DQwl antigen (DR2 associated) was found in Scottish MS patients (11), but this finding has not been confirmed (12,40). An association with the DPw4 specificity has been reported in Swedish MS patients (41).…”

Section: Discussionmentioning

confidence: 88%

“…It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4,6), prognosis with regard to degree of disability (4,7) and to mortality (8), and response to immunosuppression (9). Efforts to differentiate between PCP MS and R/R MS by serological HLA class II typing have yielded divergent and inconclusive results (10)(11)(12) (16)(17)(18).…”

mentioning

confidence: 99%

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Olerup

Hillert

Fredrikson

et al. 1989

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

220

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HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes.Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotpe. In addition, primarily chronic progressive MS was positively associated with theDQBl restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQBI allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQBI allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers ofeach clinical form ofMS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS (4,5); i.e., the disease has a continuous progressive evolution from onset. It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4, 6), prognosis with regard to degree of disability (4, 7) and to mortality (8), and response to immunosuppression (9 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…disorders [6,56,57], while estrogens have been shown to affect immune responses [13] and mast cell secretion [47][48][49][50], For instance, mast cells arc thought to participate in the pathophysiology of vascular headaches [10,54], which are more frequent in women than in men and which may also be associated with food allergy [58,59], Other neuroimmunoendocrine diseases, such as multiple sclero sis, have also been associated with mast cells [11], occur more frequently in females [60,61], and multiple sclerosis patients also have a higher incidence of migraine head aches [62]. Increased numbers of mast cells have also been found in the painful bladder disorder interstitial cystitis [9], as well as in urticaria and angioedema [63], both of which occur more frequently in women.…”

Section: Discussionmentioning

confidence: 99%

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion

Vliagoftis

Dimitriadou

Boucher

et al. 1992

Int Arch Allergy Immunol

150

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Mast cells have been studied extensively for their involvement in allergic reactions, where they secrete numerous powerful mediators in response to immunoglobulin E and specific antigens. However, they are also triggered by neuropeptides, they have been found in close contact with neurons, and they are activated in diseases such as angioedema, interstitial cystitis and irritable bowel disease, the prevalence of which is much higher in women. When tested on purified rat peritoneal mast cells, 17β-estradiol augmented secretion of histamine and serotonin, starting at 1 μM and in a dose-dependent manner, whether stimulated by the mast cell secretagogue compound 48/80 or the neuropeptide substance P. However, 17β-estradiol did not augment mast cell secretion stimulated by immunoglobulin E and specific antiserum indicating that immunologic stimulation is under different regulation. Testosterone inhibited secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibited serotonin and histamine release from purified rat peritoneal mast cells triggered by compound 48/80 or substance P. Tamoxifen also inhibited the increase in intracellular free Ca²⁺ originating from an influx of extracellular Ca²⁺ in response to compound 48/80. Moreover, tamoxifen antagonized the synergistic effect of phorbol myristate and the cation ionophore A23187 on mast cell secretion, suggesting that tamoxifen’s inhibition may be due to regulation of protein kinase C activity. Tamoxifen may, therefore, have a beneficial effect in other neuroimmunoendocrine disorders both through estrogen receptor blockade and inhibition of mast cell secretion.

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Sex distribution, age of onset and HLA profiles in two types of multiple sclerosis

Cited by 77 publications

References 19 publications

HLA antigens in Italian multiple sclerosis patients

HLA antigens in Italian multiple sclerosis patients

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion

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