Correlation between the Severity of Clinicopathological Parameters and Whole Blood Interferon-α Production Capacity in Active Phase IgA Nephropathy Patients

Abstract

Background/Aims: Patients with IgA nephropathy (IgA-N) are thought to have immune system disorders that frequently result in high serum IgA levels and a relatively high susceptibility to upper respiratory infections. Aims: To clarify the influence of the specific immune response of IgA-N patients on the clinicopathological features of the disease, we measured the whole-blood-producing capacity of interferon-α (IFNα-PC). We then compared these findings with clinical and histopathological parameters, including tissue macrophage infiltration, during both histologically active and latent phases. Patients and Methods: Fifty-one inpatients with IgA-N and 70 healthy controls were examined. According to the histological findings, 32 patients had disease in the active phase (AP), and 19 were in the latent phase (LP). Results: In AP patients, IFNα-PC showed positive correlations to serum creatinine, blood urea nitrogen, serum β₂-microglobulin (s-β₂MG), urinary total protein (U-TP), and urinary β₂MG, in addition to the number of infiltrated macrophages per area of interstitium. In LP patients, negative correlations were shown between IFNα-PC and s-β₂MG, U-TP, and U-N-acetyl-β-D-glucosaminidase. Conclusion: A significant positive relationship exists between IFNα-PC and the clinicopathological parameters of deteriorated renal lesions in the AP but not in the LP. Thus, the immune status influencing the functional damage may differ between these two phase.

Impairment of IFN-α production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma

“…In our previous studies, we have reported that IFN-α production was somehow decreased in patients with lung cancer, MDS, pulmonary tuberculosis, HIV infection, diabetes mellitus and IgA nephritis [12,13] , suggesting that IFN-α production capacity is impaired by various diseases, including cancer, infections, and metabolic disorder. In addition, periodic measurements of IFN-α production revealed decreased IFN-α production capacities in patients with lung [12] .…”

“…Several investigators have discussed the impairment of NK cell function, cytotoxic T lymphocyte (CTL) function and dendritic cell (DC) function in hepatitis C patients [8][9][10][11] . In previous papers, we have reported about the impairment of HVJ induced IFN-α production in whole blood cultures of patients with lung cancer, mylodysplastic syndrome, pulmonary tuberculosis, HIV, diabetes mellitus and IgA nephritis [12,13] . Additionally, we mentioned that IFN-α production in patients with lung cancer gradually decreases with the progress of cancer [12] .…”

Pharmacokinetic-Pharmacodynamic Modeling of Alpha Interferon Response Induced by a Toll-Like 7 Receptor Agonist in Mice

“…This would be consistent with the documented spectrum of cytokines released by peripheral blood mononuclear cells upon challenge with TLR-7 agonists (2, 34). Interestingly, a survey of the available literature revealed that across a number of studies, a typical maximum response in humans (determined via antiviral bioassays) was ϳ10,000 IU of IFN/ml (17,33,38), and therefore, maximum IFN responses appear not to be grossly different between mice and humans.…”

IFN production ability and healthy ageing: mixed model analysis of a 24 year longitudinal study in Japan

“…[22][23][24][25][26] In addition, based on records from a 17-year follow-up study (data are a part of the 24-year database), a comparison of age-matched healthy individuals and HCV patients revealed that impairment of IFN-α production was likely linked to an increase in the cancer risk. 25 Furthermore, we also showed that IFN-α production decline was not only evident in lung cancer and HCV patients but also evident in patients who developed diabetes mellitus.…”