<scp>HLA</scp> and disease: guilt by association

Howell, W. M.

doi:10.1111/iji.12088

Cited by 60 publications

(46 citation statements)

References 97 publications

(108 reference statements)

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“…Many of the immunological diseases that occur with AIH, namely autoimmune thyroiditis, RA, Sjogren's syndrome and IBD have been associated with this extended haplotype [30][31][32][33][34][35][36] . The clustering of the CAIDs in AIH may suggest the shared genetic and immunological susceptibility [37,38] . In a series of 122 patients with type 1 AIH, HLA-DR4 was significantly more common in those with CAIDs than in those without these features (62 vs. 33%, p = 0.01) [23] .…”

Section: Effects Of Aih Types Age Gender and Genetic Backgroundmentioning

confidence: 99%

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Wong

Heneghan²

2015

Dig Dis

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For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant ‘autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently described. Other conditions have been reported at a lower frequency, including Sjogren's syndrome 1-7%, systemic lupus erythematosus 1-3% and glomerulonephritis 1%. Rarer still and at a frequency of <1% include fibrosing alveolitis, haemolytic anaemia, uveitis, mononeuritis multiplex, polymyositis and multiple sclerosis. In contrast, the reported associations between AIH and thyroiditis 8-23%, diabetes 1-10% and psoriasis 3% are commonly seen and notable in clinical practice.

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Section: Effects Of Aih Types Age Gender and Genetic Backgroundmentioning

confidence: 99%

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Wong

Heneghan²

2015

Dig Dis

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“…These associations involve malignant as well as autoimmune diseases, including the well-known association between HLA-B27 and ankylosing spondylitis. Over time, several hundred diseases have been reported to occur more frequently in individuals with particular HLA genotypes (2). These diseases include a broad spectrum of immune-mediated diseases involving all major organ systems, certain malignancies, infectious diseases and, more recently, adverse reactions to particular drugs (2).…”

Section: Introductionmentioning

confidence: 99%

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Ansary

Mohammed

Hassan

et al. 2014

Molecular and Clinical Oncology

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Abstract. Similar to autoimmune diseases, there are clear associations between resistance or susceptibility to cancer and the classic human leukocyte antigen (HLA) profile of an individual. HLA-associated susceptibility to childhood acute lymphoblastic leukemia (ALL) may provide clues to leukemogenesis in general and to the role of other risk factors. The present study aimed to determine the association between the HLA-DRB1 genotype and susceptibility to ALL in children and to assess the prognostic value of HLA-DRB1 alleles in these patients. This study included 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to full clinical history, thorough clinical examination and routine laboratory investigations. Molecular HLA-DRB1 typing for patients and controls using the reverse sequence-specific oligonucleotide probe technique was performed. HLA-DRB1*04 allele frequency was significantly higher in female patients compared to that in female controls (P=0.03) and in patients aged <10 years compared to those aged ≥10 years at the time of diagnosis (P= 0.01). HLA-DRB1*11 allele frequency was significantly higher in high-risk compared to standard-risk patients (P= 0.01) and in refractory patients compared to those who achieved remission (P= 0.02). In conclusion, the HLA-DRB1*04 allele appears to be a female-specific susceptibility factor for the acquisition of childhood ALL and it may affect the age of onset of ALL. In addition, the HLA-DRB1*11 allele may be of prognostic significance in childhood ALL. However, further larger studies are required to support the conclusions drawn from this study. IntroductionAcute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing one quarter of all pediatric cancers worldwide (1).Over 40 years since the first associations between particular human leukocyte antigen (HLA) profiles and disease susceptibility were described, the identification of large numbers of HLA-associated diseases parallels our improved understanding of the genetic complexity of the HLA system and its extensive polymorphism. These associations involve malignant as well as autoimmune diseases, including the well-known association between HLA-B27 and ankylosing spondylitis. Over time, several hundred diseases have been reported to occur more frequently in individuals with particular HLA genotypes (2). These diseases include a broad spectrum of immune-mediated diseases involving all major organ systems, certain malignancies, infectious diseases and, more recently, adverse reactions to particular drugs (2).One of the factors that may determine whether a child develops ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of HLA genes, an association between an HLA allele and ALL may provide support for an infectious etiology (3).The biological significance of the associati...

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“…Alternatively, HLA may play a causative role via influence on the T-cell repertoire, including T regulatory cells, resulting in potential autoreactivity. Finally, the associated HLA polymorphism may play no direct role, merely acting as a marker [8,[24][25][26]. Studies in other populations gave varying results.…”

Section: Discussionmentioning

confidence: 99%

Association of HLA-DQB1∗06 with susceptibility to systemic lupus erythematosus in Egyptians

Mokbel

Al-Zifzaf

El-Sawy

et al. 2015

The Egyptian Rheumatologist

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Aim of the work: This study was conducted to compare the HLA-DQB1*06 allele frequency among Egyptian SLE patients and controls. The association of that allele with clinical features and distinct autoantibody profiles in SLE patients was also assessed.Patients and methods: This study included 48 consecutive Egyptian SLE patients and 49 age and sex matched unrelated healthy Egyptian subjects as a control group. All patients underwent full history taking, thorough clinical examination, SLE cumulative organ damage was scored using the Systemic Lupus International Collaborating Clinics (SLICC) damage index. Routine laboratory investigations were done as well Genomic DNA amplification by polymerase chain reaction with sequence-specific primers technique (PCR-SSP) to detect HLA DQB1*6.Results: HLA-DQB1*06 was significantly more frequent among the SLE patients. Our results showed HLA-DQB1*06 to be associated with SLE (39.6% in patients and 8.2% in controls, OR = 7.23; 95% CI = 2.22-23.6; P = .00). We found no association with the clinical findings or antibodies found in our patients apart from a significant negative association with vasculitis.

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HLA and disease: guilt by association

Cited by 60 publications

References 97 publications

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Association of Extrahepatic Manifestations with Autoimmune Hepatitis

Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Association of HLA-DQB1∗06 with susceptibility to systemic lupus erythematosus in Egyptians

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