HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population

Al-Shammri, Suhali; Nelson, Robert F.; Al-Muzairi, I; Akanji, Abayomi O.

doi:10.1191/1352458504ms1065oa

Cited by 20 publications

(17 citation statements)

References 21 publications

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“…20 Like other HLA class II alleles, the presence or absence of HLA DR15 has been implicated in several autoimmune states. [21][22][23][24][25][26][27][28][29][30][31][32][33] The precise relevance of these associations is unknown in the context of BMT.…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Battiwalla

Hahn

Radovic

et al. 2006

Blood

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The DR15 allele at the HLA DRB1 locus is a marker for immune-mediated bone marrow failure syndromes. We hypothesized that HLA DR15 plays a role in T-cell interactions with hematopoiesis and investigated the role of HLA DR15 on graftversus-host disease (GVHD) and graftversus-leukemia effects in HLA-matched allogeneic blood or marrow transplantation (BMT) performed for myeloid malignancies. We performed a retrospective analysis of 119 consecutive related and 48 consecutive unrelated allogeneic BMT for myeloid malignancies treated between 1991 and 2005 to investigate the influence of HLA DR15 on overall survival (OS), progression-free survival (PFS), and incidence of grades II to IV acute GVHD. HLA DR15 was determined by either molecular (n ‫؍‬ 108) or serologic (n ‫؍‬ 59) methods. The incidence of HLA DR15 was similar to the general white population (35/167 ‫؍‬ 21%). There were no significant differences in transplantation characteristics between the HLA DR15-positive and -negative groups. There was no significant difference in chronic GVHD, OS, or PFS between the HLA DR15-positive versus-negative groups in any disease or donor relation subgroups. The HLA DR15-positive group experienced a significantly lower incidence of acute GVHD grades II to IV: 23% versus 42% (P ‫؍‬ .041). These results suggest that HLA DR15 reduces the risk of acute GVHD. (Blood.

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Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Battiwalla

Hahn

Radovic

et al. 2006

Blood

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“…Thus, the key to observing sex differences among cytokines that distinguish between Th1 responses and Th2 responses in MS is the use of myelin-specific antigens. It is important to note that several studies have reported an association between HLA DR2 (DRB1*1502 and *0501) and female gender in MS (Al-Shammri et al, 2004;Duquette et al, 1992;Fukazawa et al, 2000;Van et al, 1986), highlighting the importance of studying male and female patients separately. We were not trying to repeat these studies, but rather to assess whether our genderskewed cytokine responses can be explained by a disproportionate representation of HLA alleles in our MS patient cohort.…”

Section: Discussionmentioning

confidence: 99%

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

Moldovan

Cotleur

Zamor

et al. 2008

Journal of Neuroimmunology

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Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients. Here, using the ELISPOT assay, we examined sex differences in single-cell secretion of Th1 and Th2 cytokines from freshly isolated PBMC between relapsing remitting (RR) MS patients and healthy individuals. Cells were stimulated with MS-associated antigens including proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and nondisease related antigens. Our data show a sex bias in the cytokine responses to multiple MS-relevant myelin antigens: Women with MS show IFNγ-skewed responses and men with MS show IL-5-skewed responses. These data extend our previous findings (Pelfrey et al., 2002): (1) by demonstrating gender skewing in cytokine responses to an expanded myelin antigen repertoire, which includes MBP, MOG and PLP; (2) by showing TNFα and IL-10 do not display comparable gender skewing compared to IFNγ and IL5; (3) by defining the patient population as early, untreated RR MS patients to avoid confounding factors, such as different disease stages/disability and immunomodulatory therapy; and (4) by showing HLA type does not appear to underlie the gender differences. These findings may explain increased susceptibility to MS in women and could contribute to the differences in disease severity between men and women.

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“…The interaction of HLA‐DQB1*03:01 with HLA‐DQB1*03:02 has been associated with MS in a large registry of European patients as well as in Olmsted County, Minnesota . Smaller population studies in Sardinia, the Basque region, Kuwait and Korea have showed similar increased susceptibility to MS in individuals expressing HLA‐DQB1*03:01 . A Swedish study and French‐Canadian study, however, found a protective role in haplotypes containing the HLA‐DQB1*03:01 allele .…”

Section: Bp and Neurologic Diseasementioning

confidence: 99%

A multi‐hit hypothesis of bullous pemphigoid and associated neurological disease: Is HLA‐DQB103:01*, a potential link between immune privileged antigen exposure and epitope spreading?

Amber

Zikry

Hertl

2017

HLA

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Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of HLA‐DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease. In our proposed multi‐hit hypothesis, patients with underlying neuronal disease are exposed to previously sequestered self‐antigen, most importantly BP180. Patients with the HLA‐DQB1*03:01 allele show an increased T‐cell avidity to several epitopes of BP180, particularly the BP180‐NC16a domain. Thus, they have a genetic susceptibility to developing BP upon exposure to the target antigen. In a patient with dysregulation of Th1/Th2 balance, anergy is lost and T‐cells are subsequently primed resulting in the development of functional autoimmunity against the BP180‐NC16a domain leading to clinically overt disease.

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HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population

Cited by 20 publications

References 21 publications

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

A multi‐hit hypothesis of bullous pemphigoid and associated neurological disease: Is HLA‐DQB103:01*, a potential link between immune privileged antigen exposure and epitope spreading?

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HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population

Cited by 20 publications

References 21 publications

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

A multi‐hit hypothesis of bullous pemphigoid and associated neurological disease: Is HLA‐DQB1*03:01, a potential link between immune privileged antigen exposure and epitope spreading?

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Product

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A multi‐hit hypothesis of bullous pemphigoid and associated neurological disease: Is HLA‐DQB103:01*, a potential link between immune privileged antigen exposure and epitope spreading?