High Prevalences of HLA—B15 and HLA—Dw6 in Patients with Cryptogenic Fibrosing Alveolitis

Varpela, E; Tiilikainen, A; Varpela, Markus; Tukiainen, P

doi:10.1111/j.1399-0039.1979.tb00824.x

Cited by 29 publications

(7 citation statements)

References 6 publications

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“…Moreover, only two of these early serologic-based determinations examined even a very restricted repertoire of the many, since-discovered, Class II alleles [44], [45]. Furthermore, diagnostic criteria for IPF have evolved considerably during the intervening years [1], raising potential concerns about the case definitions of the earlier study populations.…”

Section: Discussionmentioning

confidence: 99%

The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

et al. 2011

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients.Methods/Principal FindingsHLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3–2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036).Conclusions/SignificanceDRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease.

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Section: Discussionmentioning

confidence: 99%

The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

et al. 2011

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“…Varpela reported that high prevalences of HLA-B15 in patients with cryptogenic fibrosing alveolitis in 1979. 11 And in 1983 Libby 12 reported an increase frequency of HLA-A03 was observed in Caucasian IPF patients. Although we study the patients from different ethnic origin, these two results coincide with our findings.…”

Section: Validation Of the Findingsmentioning

confidence: 98%

HLA-A and HLA-B gene polymorphism and idiopathic pulmonary fibrosis in a Han Chinese population

Zhang

et al. 2012

Respiratory Medicine

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“…The numbers of subjects among those investigations were also usually quite small (Table 4), severely limiting their power to detect intergroup differences. Despite these potential limitations, however, several of those earlier investigations indicated HLA allele frequency perturbations may be present in IPF [40,[43][44][45], although this finding was not invariable [41,42]. In particular, one of these earlier studies indicated that DR2, a serologic correlate of HLA-DRB1*15 and, generally much less frequently, HLA-DRB1*16 gene products, appeared to be over-represented in IPF subjects (45), a finding which may be congruent with the current results.…”

Section: Discussionmentioning

confidence: 99%

“…Because of the very strong LD within this haplotype, it is difficult to precisely identify the particular disease-associated HLA allele among them, or distinguish the contributions of these HLA from other interspersed immunoregulatory elements, in lieu of focused, high-resolution genomic studies [21,38,39]. Almost all previous HLA characterizations of IPF patients date from before the development of precise and definitive molecular methodologies that distinguish these alleles [40][41][42][43][44][45] (Table 4). Moreover, only two of these early serologic-based determinations examined even a very restricted repertoire of the many, sincediscovered, Class II alleles [44,45].…”

Section: Discussionmentioning

confidence: 99%

“…Almost all previous HLA characterizations of IPF patients date from before the development of precise and definitive molecular methodologies that distinguish these alleles [40][41][42][43][44][45] (Table 4). Moreover, only two of these early serologic-based determinations examined even a very restricted repertoire of the many, sincediscovered, Class II alleles [44,45]. Furthermore, diagnostic criteria for IPF have evolved considerably during the intervening years [1], raising potential concerns about the case definitions of the earlier study populations.…”

Section: Discussionmentioning

confidence: 99%

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The HLA Class II Allele DRB1*1501 Is Over-Represented In Patients With Idiopathic Pulmonary Fibrosis

Xue¹,

Gochuico²,

Feghali‐Bostwick³

et al. 2011

C32. Studies of Lung Fibrosis, Copd and Airway Remodeling

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Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients.

show abstract

High Prevalences of HLA—B15 and HLA—Dw6 in Patients with Cryptogenic Fibrosing Alveolitis

Cited by 29 publications

References 6 publications

The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

HLA-A and HLA-B gene polymorphism and idiopathic pulmonary fibrosis in a Han Chinese population

The HLA Class II Allele DRB1*1501 Is Over-Represented In Patients With Idiopathic Pulmonary Fibrosis

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