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  • Title: Immunohistochemical and T-cell receptor gene rearrangement analyses as predictors of morbidity and mortality in refractory celiac disease.
    Author: Arguelles-Grande C, Brar P, Green PH, Bhagat G.
    Journal: J Clin Gastroenterol; 2013 Aug; 47(7):593-601. PubMed ID: 23470642.
    Abstract:
    BACKGROUND: Classification of refractory celiac disease (RCD) is based on the presence or absence of monoclonal expansions of intraepithelial lymphocytes (IELs) with an aberrant immunophenotype. GOALS: To investigate the contribution of IEL parameters toward mortality and morbidity in RCD. STUDY: IEL phenotype by immunohistochemistry and T-cell receptor (TCR) gene rearrangement by polymerase chain reaction were assessed in 73 RCD patients (type I=67, type II=6). Detection of a monoclonal TCR gene rearrangement and presence of <50% CD3 CD8 IELs were considered abnormal. Time to worsening of clinical symptoms and predictors of worsening were calculated by Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Fewer than 50% CD3 CD8 IELs were detected in 30 patients and monoclonal TCR rearrangements in 6. Three patients died and 40 suffered clinical worsening despite treatment. Estimated 5-year survival rates decreased from 100% in patients with >50% CD3 CD8 IELs and polyclonal TCR to 88% and 50% in patients with <50% CD3 CD8 IELs and monoclonal TCR, respectively. Clinical worsening was more frequent (100%) among patients harboring a monoclonal TCR gene rearrangement with <50% CD3 CD8 IELs. These patients also showed shorter median time to clinical worsening (11 mo) when compared to patients with <50% CD3 CD8 IELs alone (21 mo), polyclonal TCR (38 mo), or >50% CD3 CD8 IELs alone (66 mo). After adjusting for age and gender, only the presence of <50% CD3 CD8 IELs was associated with increased risk for clinical worsening despite negative celiac serologies (hazard ratio=4.879; 95% confidence interval, 1.785-13.336; P=0.002). CONCLUSIONS: Presence of <50% CD3 CD8 IELs is a risk factor for clinical worsening in RCD and combined with a monoclonal TCR gene rearrangement result is associated with increased mortality. IEL phenotype and TCR gene rearrangement analyses provide differential information regarding morbidity and mortality in RCD.
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