Advertisement
IMMUNOPATHOLOGY| Volume 55, ISSUE 3, P391-396, April 2023

Download started.

Ok

Serum protein electrophoresis and rheumatoid factor analysis is an effective screening strategy for cryoglobulinaemia

Published:December 06, 2022DOI:https://doi.org/10.1016/j.pathol.2022.09.004

      Summary

      Accurate serum cryoglobulin detection is important to allow prompt treatment but laboratory testing requires stringent pre-analytical conditions and has long turnaround times. Serum protein electrophoresis (EPG) for paraproteinaemia and rheumatoid factor (RF) analysis may offer an effective initial screening strategy for the presence of cryoglobulinaemia. We retrospectively assessed the sensitivity of ancillary EPG and RF testing for the presence of serum cryoglobulinaemia in 586 eligible cryoglobulin positive samples received at the Royal Prince Alfred and Liverpool Hospital immunopathology laboratories over an 11-year period. Ninety-one percent of all cryoglobulin positive samples had either a detectable paraprotein or RF activity, with greatest sensitivity for type I and type II cryoglobulins (97% and 98%, respectively). The sensitivity remained high irrespective of whether EPG and RF analysis was performed with the same, or different, pre-analytical collection conditions to the cryoglobulin collection (92% vs 90%, p=0.46). Only two patients with detected cryoglobulins and no associated paraprotein or RF activity had clinical features of cryoglobulinaemia and neither required treatment. This study demonstrates that serum EPG and RF analysis has high sensitivity for the detection of clinically relevant cryoglobulinaemia, even when not collected under ideal pre-analytical conditions, and potentially offers a prompt and effective screening strategy.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Pathology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Muchtar E.
        • Magen H.
        • Gertz M.A.
        How I treat cryoglobulinemia.
        Blood. 2017; 129: 289-298
        • Brouet J.-C.
        • Clauvel J.-P.
        • Danon F.
        • et al.
        Biologic and clinical significance of cryoglobulins: a report of 86 cases.
        Am J Med. 1974; 57: 775-788
        • Silva F.
        • Pinto C.
        • Barbosa A.
        • et al.
        New insights in cryoglobulinemic vasculitis.
        J Autoimmun. 2019; 105102313
        • Motyckova G.
        • Murali M.
        Laboratory testing for cryoglobulins.
        Am J Hematol. 2011; 86: 500-502
        • Sargur R.
        • White P.
        • Egner W.
        Cryoglobulin evaluation: best practice?.
        Ann Clin Biochem. 2009; 47: 8-16
        • Vermeersch P.
        • Gijbels K.
        • Mariën G.
        • et al.
        A critical appraisal of current practice in the detection, analysis, and reporting of cryoglobulins.
        Clin Chem. 2008; 54: 39-43
        • Roccatello D.
        • Saadoun D.
        • Ramos-Casals M.
        • et al.
        Cryoglobulinaemia Nat Rev Dis Primers. 2018; 4: 11
        • Vita S.D.
        • Soldano F.
        • Isola M.
        • et al.
        Preliminary classification criteria for the cryoglobulinaemic vasculitis.
        Ann Rheum Dis. 2011; 70: 1183-1190
        • Warren J.S.
        Clinically unsuspected cryoglobulinemia: cases that present as laboratory artifact.
        Am J Clin Pathol. 2013; 139: 352-359
        • Jiang J.X.
        • Kakar F.
        • Wing H.
        • et al.
        The case of the interfering IgM.
        Pathology. 2017; 49: 455-457
        • Dammacco F.
        • Sansonno D.
        • Piccoli C.
        • et al.
        The cryoglobulins: an overview.
        Eur J Clin Invest. 2001; 31: 628-638
        • Braun G.S.
        • Horster S.
        • Wagner K.S.
        • et al.
        Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects.
        Postgrad Med J. 2007; 83: 87
        • Terrier B.
        • Karras A.
        • Kahn J.-E.
        • et al.
        The spectrum of type I cryoglobulinemia vasculitis.
        Medicine. 2013; 92: 61-68
        • Pietrogrande M.
        • Corona M.
        • Milani S.
        • et al.
        Relationship between rheumatoid factor and the immune response against hepatitis C virus in essential mixed cryoglobulinemia.
        Clin Exp Rheumatol. 1995; 13: S109-S113
        • Voma C.B.
        • Levinson S.S.
        Analysis, detection and quantitation of mixed cryoglobulins in HCV infection: brief review and case examples.
        Clin Chem Lab Med. 2016; 54: 1853-1859
        • Chen Y.P.
        • Cheng H.
        • Rui H.L.
        • et al.
        Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice.
        Chin Med J. 2019; 132: 1723-1732
        • Kallemuchikkal U.
        • Gorevic P.D.
        Evaluation of cryoglobulins.
        Arch Pathol Lab Med. 1999; 123: 119-125
        • Bryce A.H.
        • Kyle R.A.
        • Dispenzieri A.
        • et al.
        Natural history and therapy of 66 patients with mixed cryoglobulinemia.
        Am J Hematol. 2006; 81: 511-518
        • Shihabi Z.K.
        Cryoglobulins: an important but neglected clinical test.
        Ann Clin Lab Sci. 2006; 36: 395-408
        • Trejo O.
        • Ramos-Casals M.
        • Garcia-Carrasco M.
        • et al.
        Cryoglobulinemia Med. 2001; 80: 252-262
        • Saadoun D.
        • Landau D.A.
        • Calabrese L.H.
        • et al.
        Hepatitis C-associated mixed cryoglobulinaemia: a crossroad between autoimmunity and lymphoproliferation.
        Rheumatology. 2007; 46: 1234-1242
        • Kolopp-Sarda M.N.
        • Cryoglobulins Miossec P.
        An update on detection, mechanisms and clinical contribution.
        Autoimmun Rev. 2018; 17: 457-464
        • Natali P.
        • Galassi G.
        • Debbia D.
        • et al.
        Frequency and results of cryoglobulin retesting in 4,963 patients: comment on the article by Kolopp-Sarda.
        al Arthritis Rheumatol. 2020; 72 (–6): 1955
        • Kolopp-Sarda M.N.
        • Nombel A.
        • Miossec P.
        Cryoglobulins today: detection and immunologic characteristics of 1,675 positive samples from 13,439 patients obtained over six years.
        Arthritis Rheumatol. 2019; 71: 1904-1912
        • Ferri C.
        • Sebastiani M.
        • Giuggioli D.
        • et al.
        Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients.
        Semin Arthritis Rheum. 2004; 33: 355-374
        • Gorevic P.D.
        • Kassab H.J.
        • Levo Y.
        • et al.
        Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients.
        Am J Med. 1980; 69: 287-308