Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong.

The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screening (NBS) programs for Severe Combined Immunodeficiency. The potential applications of combined TREC and KREC assay in PIDD diagnosis and immune reconstitution monitoring in non-neonatal patients have been suggested. Given that ethnicity, gender, and age can contribute to variations in immunity, defining the reference intervals of TREC and KREC levels in the local population is crucial for setting up cut-offs for PIDD diagnosis. In this retrospective study, 479 healthy Chinese sibling donors (240 males and 239 females; age range: 1 month-74 years) from Hong Kong were tested for TREC and KREC levels using a simultaneous quantitative real-time PCR assay. Age-specific 5th-95th percentile reference intervals of TREC and KREC levels (expressed in copies per µL blood and copies per 106 cells) were established in both pediatric and adult age groups. Significant inverse correlations between age and both TREC and KREC levels were observed in the pediatric age group. A significant higher KREC level was observed in females than males after 9-12 years of age but not for TREC. Low TREC or KREC levels were detected in patients diagnosed with mild or severe PIDD. This assay with the established local reference intervals would allow accurate diagnosis of PIDD, and potentially monitoring immune reconstitution following haematopoietic stem cell transplantation or highly active anti-retroviral therapy in the future.

Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase.

UNLABELLED: In view of the findings that high hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is associated with increased risk of chronic hepatitis B (CHB)-related complications, disease progression in CHB patients in the immune-tolerant phase is uncertain. We evaluated disease progression in 57 immune-tolerant CHB patients with high HBV DNA. Each subject underwent an initial liver biopsy. In those who remained in the immune-tolerant phase, a follow-up liver biopsy was performed after 5 years of follow-up. Patients who developed elevated serum alanine aminotransferase (ALT) levels were discontinued from the study after a follow-up liver biopsy. Disease progression was defined as a 1-point increase in fibrosis stage. Initial liver biopsies showed the median fibrosis stage of the study patients was 1 (range 0-1). By the end of follow-up, 9 of the 57 patients (15.8%) had developed elevated serum ALT. In those who remained in the immune-tolerant phase, follow-up fibrosis stage was comparable with the initial fibrosis stage (P = 0.58). However, disease progression was greater in patients who developed elevated serum ALT when compared with those who remained in the immune-tolerant phase (5 of 9 vs. 3 of 48, respectively, P = 0.001). The median rate of fibrosis progression of patients who remained in the immune-tolerant phase was lower than that of patients with high serum ALT (0 U/year [range -0.40-0.20 U/year] versus 0.21 U/year [range 0-1.11 U/year], respectively, P = 0.04). CONCLUSION: CHB patients in the immune-tolerant phase have mild disease. In those who remained in the immune-tolerant phase in the present study, disease progression was minimal. However, immune-tolerant patients who progressed to the immune clearance phase often faced disease progression.