Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection

D. Roccatello, G. Morsica, G. Picciotto, G. Cesano, R. Ropolo, M. T. Bernardi, G. Cacace, G. Cavalli, L. M. Sena, A. Lazzarin, G. Piccoli, A. Rifai

Research output: Contribution to journalArticle

Abstract

The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor-IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30-300s after injection, only a minor fraction (<15%) of the circulating cryoglobulins bound to the erythrocytes, suggesting the elimination mechanisms are independent of binding to CRI on erythrocytes. The overall blood disappearance curve showed a fast (≤ 1 min) and slow (> 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P <0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM-IgG-HCV complexes may underlie their renal deposition.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalClinical and Experimental Immunology
Volume110
Issue number1
Publication statusPublished - 1997

Fingerprint

Cryoglobulins
Cryoglobulinemia
Virus Diseases
Hepacivirus
Nephritis
Liver
Kidney
Immunoglobulin M
Immunoglobulin G
Serum
RNA
Membranoproliferative Glomerulonephritis
Mononuclear Phagocyte System
Gamma Cameras
Rheumatoid Factor
Radionuclide Imaging
Radioactivity
Spleen
Control Groups
Injections

Keywords

  • Cryoglobulins
  • Liver
  • Nephritis
  • Scintigraphy
  • Spleen

ASJC Scopus subject areas

  • Immunology

Cite this

Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection. / Roccatello, D.; Morsica, G.; Picciotto, G.; Cesano, G.; Ropolo, R.; Bernardi, M. T.; Cacace, G.; Cavalli, G.; Sena, L. M.; Lazzarin, A.; Piccoli, G.; Rifai, A.

In: Clinical and Experimental Immunology, Vol. 110, No. 1, 1997, p. 9-14.

Research output: Contribution to journalArticle

Roccatello, D, Morsica, G, Picciotto, G, Cesano, G, Ropolo, R, Bernardi, MT, Cacace, G, Cavalli, G, Sena, LM, Lazzarin, A, Piccoli, G & Rifai, A 1997, 'Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection', Clinical and Experimental Immunology, vol. 110, no. 1, pp. 9-14.
Roccatello, D. ; Morsica, G. ; Picciotto, G. ; Cesano, G. ; Ropolo, R. ; Bernardi, M. T. ; Cacace, G. ; Cavalli, G. ; Sena, L. M. ; Lazzarin, A. ; Piccoli, G. ; Rifai, A. / Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection. In: Clinical and Experimental Immunology. 1997 ; Vol. 110, No. 1. pp. 9-14.
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AU - Cesano, G.

AU - Ropolo, R.

AU - Bernardi, M. T.

AU - Cacace, G.

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