IgA deficiency occurs in 1.7%–2.6% of CD patients, which represents a 10–15-fold

increase over that in the general population.39 In these individuals, the IgA antibody tests are falsely negative. In our study 2.2% (2/91) of first-degree relatives were IgA-deficient but none had CD. In a screening study of both first- and second-degree relatives of subjects with CD, where total IgA was estimated in relatives who were IgA-tTGA-negative and IgG-tTGA-positive, Fraser et al. found that 1% of the relatives were IgA-deficient.29 Two of the 42 first-degree relatives found to have CD after screening were IgA-deficient in the study by Bonamico et al.16 At our centre, the cost of HLA DQ2/DQ8 testing is $US104 and that of IgA-tTGA testing is $US6. If we compare the two methods of screening: serology is required every three years, until the age of 70 years; and HLA DQ2/DQ8 Midostaurin solubility dmso estimation is carried out at the first learn more visit and serology is required every 3 years thereafter in those who are HLA DQ2/8-positive (Table 4). The cost of screening all participating first-degree relatives

in our study with serology alone would be $US8388 and that of one-time HLA and then serology would be $US16 646, which is more expensive than screening by serology alone. HLA DQ2/DQ8 testing followed by serial serology testing in positive subjects has the advantage of relieving the anxiety associated with the risk of developing CD and excluding the need for repeated blood sampling and physician visits in approximately 15% of the first-degree relatives. We would recommend inclusion of HLA DQ2/DQ8 testing in screening of first-degree relatives. We support the strategy

suggested by Bonamico et al.,16 of doing HLA DQ2/DQ8 tests only in relatives who are Oxymatrine serology-negative at the first evaluation and then doing repeated serological screening only in the HLADQ2/DQ8-positive relatives to further cut down the cost related to HLA testing. In conclusion, 4.4% or one in 22 first-degree CD relatives were diagnosed to have CD. An equal number of new cases were identified in parents and siblings. Intermittent diarrhea and anemia were more common in serology-positive relatives and thus may help in identification of affected individuals in this high-risk group. Inclusion of one-time HLA DQ2/8 estimation along with serial serology in HLA-positive subjects may be useful for diagnosis and follow up of CD relatives. Physicians need to be aware that first-degree relatives represent an important group for CD in order to facilitate early diagnosis and reduce the complications of untreated disease. The study was funded by an intramural research grant from Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. There is no conflict of interest of any author. “
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