Association between Hepatitis B Virus and Essential Mixed Cryoglobulinemia

Levo, Y; Gorevic, Peter D.; Kassab, Hannah Jane; Zucker‐Franklin, Dorothea; Franklin, Edward C.

doi:10.1056/nejm197706302962605

Cited by 383 publications

(94 citation statements)

References 15 publications

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“…2,[12][13][14][15] In this regard, it is worth noting that cryoglobulinemia is frequently observed in patients with liver injuries. 36,37 This might be due to a lack of efficient elimination of asialylated IgG with cryogenic potential in these patients, because the liver is known to be the major site for removal of serum asialoglycoproteins due to the expression of the asialoglycoprotein receptor on hepatocytes. 38,39 It should be stressed that the ability of the 6-19 F243A mutant to generate IgG3 self-associating complexes was not impaired.…”

Section: Discussionmentioning

confidence: 99%

Sialylation Determines the Nephritogenicity of IgG3 Cryoglobulins

Otani

Kuroki

Kikuchi

et al. 2012

Journal of the American Society of Nephrology

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Monoclonal 6-19 IgG3 anti-IgG2a rheumatoid factor derived from lupus-prone MRL-Fas lpr mice can induce GN and cryoglobulinemia, but the features that confer nephritogenic potential are not completely understood. Asparagine-linked oligosaccharide chains of 6-19 IgG3 mAb are poorly galactosylated and hardly sialylated, possibly contributing to the pathogenic potential of 6-19 IgG3 rheumatoid factors. Here, we used the 6-19 model of cryoglobulin-associated GN to define the relative contributions of galactosylation and sialylation, in relation to cryoglobulin activity, to the nephritogenic potential of IgG3 antibodies. We generated one highly sialylated and two distinct more galactosylated 6-19 IgG3 rheumatoid factor variants. Although the mere extent of galactosylation had no effect on either the cryogenic and nephritogenic activities of 6-19 IgG3 rheumatoid factor, terminal sialylation attenuated the nephritogenic potential of 6-19 IgG3 by limiting its cryoglobulin activity. These data suggest a protective role of IgG sialylation against the development of cryoglobulin-mediated GN, highlighting the anti-inflammatory activity of sialylated IgG antibodies. Cryoglobulins are a heterogeneous group of Igs that precipitate at temperatures ,37°C, with resolution upon warming. 1,2 Most cryoglobulins are either monoclonal Ig or Ig complexes in which one component, usually IgM, has rheumatoid factor (RF) activity. 1,2 Monoclonal cryoglobulins are mainly associated with various lymphoproliferative disorders, whereas mixed cryoglobulins are often found in sera of patients with autoimmune diseases, such as SLE and rheumatoid arthritis, or with chronic infectious diseases. The presence of cryoglobulins can result in a wide range of vascular, renal, and neurologic complications, likely depending on their concentration, their temperature-dependent solubility behavior, and the nature and type of proteins involved. 2 Antibodies of the IgG3 subclass in humans and mice have the unique physicochemical property that allows them to self-associate via Fc-Fc interactions and to display cryoglobulin activity, independently of their specificities. [3][4][5][6][7][8] Nucleotide sequence analysis of the variable regions of cryogenic and noncryogenic IgG3 mAbs, in combination with the assessment of mutant antibodies, showed that cryoglobulin activity of IgG3 was associated with the presence of more positively charged amino-acid residues at positions 6 and 23 of the heavy-chain variable domain. 9,10 Moreover, structural analysis of asparagine-linked biantennary complex-type oligosaccharide chains (N-glycans) attached to the CH2 domain of different IgG3 mAbs revealed an inverse correlation

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Section: Discussionmentioning

confidence: 99%

Sialylation Determines the Nephritogenicity of IgG3 Cryoglobulins

Otani

Kuroki

Kikuchi

et al. 2012

Journal of the American Society of Nephrology

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“…A vasculite leucocitoclástica por depósitos de crioglobulinas é frequentemente associada a infecção pelo vírus da hepatite C 6,7 , sendo a sua relação com a infecção pelo vírus da hepatite B é algo controversa, havendo no entanto alguns casos relatados 8,9,10 . A presença de factor reumatóide positivo 11 e a hipocomplementémia são dados a favor da formação de imunocomplexos 12 .…”

Section: Discussionunclassified

Vasculite leucocitoclástica e infecção crónica por Hepatite B

Pires¹,

Sousa²,

Montez³

et al. 2014

Gal. Clin.

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ResumoOs autores apresentam o caso clínico de uma doente de 79 anos, internada para estudo de uma vasculite, cuja investigação etiológica nos levou a ponderar a associação com hepatite B crónica. A vasculite leucocitoclás-tica pode ter variadas etiologias. A associação com hepatite vírica é mais frequente com a hepatite C, havendo no entanto alguns casos relatados sobre a associação à hepatite B. A etiologia vírica tem de ser sempre considerada nestas situações, pois a resolução do quadro pode passar pelo tratamento da patologia de base.Palavras chave: Vasculitis leucocitoclàstica. Hepatitis B crònica. Crioglobulinas. AbstractThe authors present a case report of a 79 year old patient who was admitted for the study of vasculitis, whose etiological investigation led us to consider the association with chronic hepatitis B infection. Leucocytoclastic vasculitis may have varied etiologies. The association with viral hepatitis is more common with hepatitis C, but there are some cases reported about the association with hepatitis B. The viral etiology must always be considered in such situations because the case resolution can implicate the treatment of the underlying disease.

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“…It was hoped that the causative agent of Lyme arthritis would be seen in the cryoprecipitates from patients with ECM. In hepatitis B infection and in essential mixed cryoglobulinemia, particles suggestive of the Dane particle-an overall diameter of 42 nm, an electrondense core of 28 nm, and cross striations with a periodicity of 3 nm ( 2 4 F h a v e been seen in redissolved cryoglobulins (25,26), and in infectious mononucleosis, particles suggestive of Epstein-Barr (EB) virus have been seen (27). In 2 of 10 patients with ECM-the 2 tested earliest after onset-particles were noted in the cryoprecipitates that were somewhat reminiscent of the Dane particle (Figure 8) (neither patient had a positive test for HB,Ag or anti-HB in acute or convalescent sera).…”

Section: Discussionmentioning

confidence: 99%

Correlation of Serum and Cryoglobulin IgM with Activity, and Serum IgG with Remission

Steere

Hardin

Ruddy

et al. 1979

Arthritis & Rheumatism

121

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Forty-eight patients with erythema chronicum migrans (ECM) were studied prospectively for 6 to 18 months. Twenty-six patients had no later symptoms, but 22 subsequently developed Lyme arthritis and 9 of them also experienced neurologic abnormalities. Eighty-seven percent of patients with active ECM followed by subsequent involvement had cryoglobulins containing IgM compared to only 13% of those with active ECM and no later symptoms. The former group also had significantly lower IgG, C3, and C4 levels. Sixty-seven percent of patients still had serum cryoglobulins when neurologic disease was most active, and 45% had them when joint symptoms were most severe, but only 11% continued to have small amounts in remission. The number of patients who continued to have serum cryoglobulins with recurrent attacks of arthritis decreased with time. In contrast, patients always had cryoglobulins in joint fluid, a finding Lyme arthritis shares with rheumatoid arthritis. The cryoprecipitates from 2 of I0 patients contained particles with internal structure, but their viral nature is problematic. All components of antisera obtained from

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Association between Hepatitis B Virus and Essential Mixed Cryoglobulinemia

Cited by 383 publications

References 15 publications

Sialylation Determines the Nephritogenicity of IgG3 Cryoglobulins

Sialylation Determines the Nephritogenicity of IgG3 Cryoglobulins

Vasculite leucocitoclástica e infecção crónica por Hepatite B

Correlation of Serum and Cryoglobulin IgM with Activity, and Serum IgG with Remission

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