Abnormal protein electrophoresis without monoclonal peak (polyclonal hypergammaglobulinaemia, beta-gamma bridging, hypoalbuminaemia)
BioMG follows French guidelines. Adapt it to the guidelines and the tests available where you practise.
Raised gammaglobulins without a peak (polyclonal hypergammaglobulinaemia, "beta-gamma bridging")
Laboratory tests
- FBC
- CRP
- AST
- ALT
- GGT
- Alkaline phosphatase
- HIV serology
- Hepatitis C serology
- Hepatitis B serology (HBsAg, anti-HBs, anti-HBc)
- Antinuclear antibodies (if arthralgia, sicca syndrome, skin involvement, cytopenia or Raynaud phenomenon)if needednon-French guidelineSigns of connective tissue disease: connective tissue diseases (lupus, rheumatoid arthritis, mixed connective tissue disease, etc.) are the second cause of marked polyclonal hypergammaglobulinaemia [1,2].
- PT (if beta-gamma bridging or signs of chronic liver disease)if neededThe beta-gamma bridge is, together with hypoalbuminaemia, among the electrophoresis abnormalities that the HAS asks to look for when cirrhosis is suspected; a reduced PT is also one of them [3].
- Serum creatinine with eGFRif needednon-French guidelineNo obvious cause after the first tests: the South Tees care pathway (NHS, United Kingdom) suggests then considering renal function and serum calcium, with FBC, LFTs, CRP and autoimmune tests [4]. The HAS memo page, limited to abnormalities suggesting a monoclonal immunoglobulin, does not address this point [5].
- Serum calciumif needednon-French guidelineNo obvious cause after the first tests: the South Tees care pathway (NHS, United Kingdom) suggests then considering renal function and serum calcium, with FBC, LFTs, CRP and autoimmune tests [4]. The HAS memo page, limited to abnormalities suggesting a monoclonal immunoglobulin, does not address this point [5].
Do not order
- Immunofixation (immunotyping) requested from the outset: characterisation of an abnormality suspected to be monoclonal is done at the laboratory's initiative; a mere “restriction of gamma globulin heterogeneity”, a minor abnormality, should not lead to immunotyping [5].
- Bence Jones proteinuria: should not be requested [5].
Low albumin (hypoalbuminaemia)
Laboratory tests
- CRP
- Serum creatinine with eGFR
- AST
- ALT
- GGT
- Bilirubin
- PT (if liver disease suspected)if needednon-French guidelineSuspected liver disease (abnormal enzymes, alcohol, signs of liver disease): albumin and PT give information on the liver's synthetic function, remembering that albumin also falls in many other situations [7].
Urine tests
- Urine protein:creatinine ratio (spot sample)
- Urine dipstick in the practice (proteinuria).
Sources (12)
- Dispenzieri A, Gertz MA, Therneau TM, Kyle RA. Retrospective cohort study of 148 patients with polyclonal gammopathy. Mayo Clin Proc. 2001;76(5):476-87.
- O'Connell TX, Horita TJ, Kasravi B. Understanding and interpreting serum protein electrophoresis. Am Fam Physician. 2005;71(1):105-12.
- Haute Autorité de santé. Critères diagnostiques et bilan initial de la cirrhose non compliquée. Recommandations professionnelles (actualisation), décembre 2008.
- South Tees Hospitals NHS Foundation Trust. Polyclonal immunoglobulins / hypergammaglobulinaemia. Parcours de soins, HNY Policy and Pathway Repository (Royaume-Uni), en ligne le 10/03/2026.
- Haute Autorité de santé. Fiche mémo : Quand prescrire une électrophorèse des protéines sériques (EPS) et conduite à tenir en cas d'une immunoglobuline monoclonale. Janvier 2017 (version mise à jour après le rapport VS de novembre 2025).
- Zhao EJ, Cheng CV, Mattman A, Chen LYC. Polyclonal hypergammaglobulinaemia: assessment, clinical interpretation, and management. Lancet Haematol. 2021;8(5):e365-e375.
- Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests (British Society of Gastroenterology, Association of Clinical Biochemistry and Laboratory Medicine, British Association for the Study of the Liver). Gut. 2018;67(1):6-19.
- National Institute for Health and Care Excellence. Myeloma: diagnosis and management. NICE guideline NG35, 10 février 2016, mise à jour le 25 octobre 2018.
- National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. NICE guideline NG12, 23 juin 2015, mise à jour le 15 avril 2026.
- Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO). Onkopedia : Monoklonale Gammopathie unklarer Signifikanz (MGUS). Stand September 2026.
- Evans DC, Corkins MR, Malone A, et al.; ASPEN Malnutrition Committee. The Use of Visceral Proteins as Nutrition Markers: An ASPEN Position Paper. Nutr Clin Pract. 2021;36(1):22-28.
- Haute Autorité de santé, Fédération française de nutrition. Diagnostic de la dénutrition chez l'enfant, l'adulte et la personne de 70 ans et plus. Fiche outil, novembre 2021.