TITLE

Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy

AUTHOR(S)
De Caestecker, Mark P.; Bottomley, Martin; Telfer, Brian A.; Hutchinson, Ian V.; Vose, Brent M.; Ballardie, Francis W.
PUB. DATE
December 1993
SOURCE
Kidney International;Dec1993, Vol. 44 Issue 6, p1298
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Dysregulated cytokine expression has been implicated in the pathogeneis of IgA nephropathy, but the mechanisms and selectivity of this response are poorly understood. In this study we have examined the expression of a range of immunoregulatory cytokine mRNAs by peripheral blood mononuclear cells (PBMNCs) from 45 patients with IgA nephropathy stratified empirically according to urinary red cell excretion: 10 in remission, and 35 with active disease (21 mild, 14 moderate), and 17 normal: and 15 disease, controls. We used a semi-quantitative polymerase chain reaction (PCR) technique. None of the patients had experienced recent episodes of macroscopic hematuria. Simultaneous analysis of monocyte class II antigen (DR) expression was also performed by two-color immunoflow cytometry. TGF-β1 mRNA was detected in 68% (24 of 35) of patients with active, and 70% (7 of 10) inactive IgA nephropathy, but in only 18%, (3 of 17) normal (P < 0.005), and 27% (4 of 15) disease controls. IL-6 transcripts were identified in 37% (13 of 35) of patients with active IgA nephropathy, compared with 6% (1 of 17) normal controls (P = 0.015), with no significant increase in IgA remission, or disease control groups. TNF-α mRNA was detected in 29% (5 of 17) of normal and 53% (8 of 15) disease controls, but in only 7% (3 of 35) of patients with IgA nephropathy (P = 0.015). There was no significant change in TGF-β2, γ-IFN, IL-2, IL-4, IL-1α or IL-1β detection between groups. There was an association between γ-IFN and IL-6 mRNA detection in patients with active IgA nephropathy: 83% (5 of 6) with γ-IFN transcripts also had detectable IL-6 mRNA, compared with 28% (8 of 29) of those without γ-IFN transcripts (P = 0.01). There was also phenotypic evidence of cellular activation, with an increased percentage of monocytes expressing high levels of class II antigen in patients with moderately active nephropathy, mean (ᴅ), 12.6 (4.8)%, compared with normal, 6.7 (1.6)% (P < 0.001), and disease controls, 7.5 (5.2)%. Furthermore, class II antigen expression was significantly higher in IgA nephropathy patients with detectable IL-6, 12.4 (5.1)%, and in particular, γ-IFN mRNA, 14.3 (6.8)%, as opposed to those without detectable mRNA species. 8.8 (3.8)%, and 9.2 (3.7)%, respectively (P ≤ 0.02). These data suggest there is an abnormal interactive network of monocyte and T cell derived cytokines, associated with monocyte activation. in peripheral blood MNCs from patients with IgA nephropathy. This may have important implications for the pathogenesis of immune system abnormalities, renal cell injury and scar tissue formation in this disease.
ACCESSION #
20453434

 

Related Articles

  • Genetic Manipulation of Tumor-specific Cytotoxic T Lymphocytes to Restore Responsiveness to IL-7. Vera, Juan F.; Hoyos, Valentina; Savoldo, Barbara; Quintarelli, Concetta; Attianese, Greta M. P. Giordano; Leen, Ann M.; Hao Liu; Foster, Aaron E.; Heslop, Helen E.; Rooney, Cliona M.; Brenner, Malcolm K.; Dotti, Gianpietro // Molecular Therapy;May2009, Vol. 17 Issue 5, p880 

    Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) can induce objective clinical responses in patients with malignant diseases. The option of providing a proliferative and survival advantage to adoptively transferred CTLs remains a challenge to improve their efficacy. Host...

  • Leukocyte Function-Associated Antigen-3 (LFA-3). Vohr, Hans-Werner // Encyclopedic Reference of Immunotoxicology;2005, p384 

    An entry for "leukocyte function-associated antigen-3 (LFA-3)" is presented. It refers to a co-stimulatory molecule whose ligand is the CD2 molecule expressed on T lymphocytes. LFA-3 is involved in cytokine secretion.

  • Heterogeneity in the CD4 T Cell Compartment and the Variability of Neonatal Immune Responsiveness. Adkins, Becky // Current Immunology Reviews;2007, Vol. 3 Issue 3, p151 

    Over the past decade, it has become clear that T cell immune responses in both murine and human neonates are very heterogeneous, running the gamut from poor or deviant responsiveness to mature, adult-like inflammatory function. How this variability arises is not well understood but there is now...

  • Effect of IL–4, IFN–Á and IL–12 on Cytokine Production from Human CD45RA and CD45RO CD4 T Cell Precursors. Sasama, J.; Vyas, B.; Vukmanovic–Stejic, M.; Kemeny, D.M. // International Archives of Allergy & Immunology;Dec1998, Vol. 117 Issue 4, p255 

    The aim of this study was to compare the effects of IL–4, IL–12 and IFN–γ on the production of T helper–1 (Th1) and T helper–2 (Th2)–type cytokines from human peripheral blood 'naive' CD45RA and 'memory' CD45RO CD4 T cells. CD45RA or CD45RO CD4 T...

  • Suppression of Adiponectin by Aberrantly Glycosylated IgA1 in Glomerular Mesangial Cells In Vitro and In Vivo. Inoue, Tatsuyuki; Sugiyama, Hitoshi; Kitagawa, Masashi; Takiue, Keiichi; Morinaga, Hiroshi; Ogawa, Ayu; Kikumoto, Yoko; Kitamura, Shinji; Maeshima, Yohei; Makino, Hirofumi // PLoS ONE;Mar2012, Vol. 7 Issue 3, p1 

    The pathogenesis of IgA nephropathy (IgAN) may be associated with the mesangial deposition of aberrantly glycosylated IgA1. To identify mediators affected by aberrantly glycosylated IgA1 in cultured human mesangial cells (HMCs), we generated enzymatically modified desialylated and...

  • Suppression of Adiponectin by Aberrantly Glycosylated IgA1 in Glomerular Mesangial Cells In Vitro and In Vivo. Inoue, Tatsuyuki; Sugiyama, Hitoshi; Kitagawa, Masashi; Takiue, Keiichi; Morinaga, Hiroshi; Ogawa, Ayu; Kikumoto, Yoko; Kitamura, Shinji; Maeshima, Yohei; Makino, Hirofumi // PLoS ONE;Mar2012, Vol. 7 Issue 3, p1 

    The pathogenesis of IgA nephropathy (IgAN) may be associated with the mesangial deposition of aberrantly glycosylated IgA1. To identify mediators affected by aberrantly glycosylated IgA1 in cultured human mesangial cells (HMCs), we generated enzymatically modified desialylated and...

  • Less is more. Bird, Lucy // Nature Reviews Immunology;Apr2006, Vol. 6 Issue 4, p1 

    Presents information on research being done on in vivo T-cell survival by Marc Jenkins and colleagues published in "Sceince." Explanation that protective immunity to pathogens requires memory T cells that survive for many years after initial exposure to the infectious agent; Details on the...

  • Non-Redundant Role for IL-12 and IL-27 in Modulating Th2 Polarization of Carcinoembryonic Antigen Specific CD4 T Cells from Pancreatic Cancer Patients. Tassi, Elena; Braga, Marco; Longhi, Renato; Gavazzi, Francesca; Parmiani, Giorgio; Di Carlo, Valerio; Pia Protti, Maria // PLoS ONE;2009, Vol. 4 Issue 10, p1 

    Background: Pancreatic cancer is a very aggressive disease with dismal prognosis; peculiar is the tumor microenvironment characterized by an extensive fibrotic stroma, which favors rapid tumor progression. We previously reported that pancreatic cancer patients have a selective Th2 skew in the...

  • T Helper 1 Cytokines (Th1). Vohr, Hans-Werner // Encyclopedic Reference of Immunotoxicology;2005, p627 

    This entry provides information on the term "T Helper 1 Cytokines," of Th1. CD4 T cells produce cytokines such as IFN-∝ and IL-2, which are autocrine and paracrine signaling molecules, in response to major histocompatibility complex class II antigen stimulation, and stimulate growth and...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics