Clin Chem Lab Med 2015; aop

Letter to the Editor Bénédicte Puissant-Lubrano, Michael Peres, Pol-André Apoil, Nicolas Congy-Jolivet, Francis Roubinet and Antoine Blancher*

Immunoglobulin IgA, IgD, IgG, IgM and IgG subclass reference values in adults DOI 10.1515/cclm-2014-1186 Received December 2, 2014; accepted December 19, 2014

Keywords: healthy donors; human; immunoglobulin concentrations in blood; immunoturbidimetry; middle age. To the Editor, Immunoglobulins (Ig) are the effectors of the humoral responses toward infectious pathogens. They contribute to the control of the proliferation of pathogens by killing them through various mechanisms, such as opsonization, antibody-dependent cell-mediated cytotoxicity and complement activation. A fraction of Ig can neutralize various pathogens and their toxins. In clinical practice, the quantification of immunoglobulins and/or IgG subclasses in serum or plasma is helpful in various clinical circumstances, such as 1) diagnosis of acquired or primary immune deficiencies, including common variable immunodeficiency which occurs in young adults [1]; 2) follow-up of various therapies (i.e., Ig, immunosuppressive biotherapies, immunosuppessive chemotherapies) [2]; 3) follow-up of monoclonal gammopathy [3]. Indications of IgD quantification are restricted to IgD monoclonal gammopathy and hyper IgD syndrome [4]. In clinical laboratories, nephelometry is the reference method for the quantification of specific proteins, *Corresponding author: Pr. Antoine Blancher, Laboratoire d’Immunologie du CHU de Toulouse, Hôpital Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France, Phone: +33 5 61 323432, Fax: +33 5 61 323424, E-mail: [email protected]; and Laboratoire d’Immunogénétique Moléculaire, EA 3034, Université Paul Sabatier, Toulouse III, France Bénédicte Puissant-Lubrano, Pol-André Apoil and Nicolas CongyJolivet: Laboratoire d’Immunogénétique Moléculaire, EA 3034, Université Paul Sabatier, Toulouse III, France; and Laboratoire d’Immunologie, CHU de Toulouse, France Michael Peres: Laboratoire d’Immunologie, CHU de Toulouse, France Francis Roubinet: EFS Pyrénées-Méditerranée, Toulouse, France

including immunoglobulins. Recently, improvement of immunoturbidimetry enabled this technique to be used as an alternative to immunonephelometry. Whatever the technique, the clinical interpretation of the levels requires a confrontation to reference values. Therefore, in the present work, we define the reference values of IgA, IgD, IgG, IgM and IgG subclasses in a European population sample of healthy adults, using fully automated immunoturbidimetry standardized with the ongoing reference material (DA470k). EDTA-anticoagulated peripheral blood venous samples were collected from 270 healthy donors from Etablissement Français du Sang-Pyrénées-Méditerranée (EFS-PM). Blood donors aged from 18 to 68  years with similar number of both sexes (134 females and 136 males) and age range gave their written informed consent prior to blood sampling. Each donor filled in a questionnaire complementary to that of EFS-PM to check for the absence of infectious disease, cancer, allergy, vaccination and antiinflammatory or antibiotic treatment for 2 months. EDTA plasmas were frozen at –80 °C for a maximum period of 18 months. Immunoglobulins and IgG subclasses were measured on a SPAplus® turbidimeter (The Binding Site, Saint-Egrève, France). Assays were calibrated with the international reference material ERM-DA470k (IgG, IgA, IgM and IgG subclasses) and with the British Standard search for human immunoglobulin D NIBSC 67/037. Two levels of internal quality controls were measured in parallel with samples: they were within the range recommended by the manufacturer and met the imprecision specifications of Ricos (www.westgard.com/biodatabase1. htm). We previously reported the analytical performance of the quantification of immunoglobulins on the SPAplus® device [5]. The concentrations of IgG and IgG2 of 270 blood donors had a normal distribution while the concentrations of IgA, IgM and IgG3 displayed a log-normal distribution. The distributions of IgD, IgG1 and IgG4 were not normal and not normalized by log-transformation (Kolmogorov-Smirnov test).

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2      Puissant-Lubrano et al.: Immunoglobulin and IgG subclass values in healthy individuals

IgM concentrations were found to be higher in females than in males (p 

Immunoglobulin IgA, IgD, IgG, IgM and IgG subclass reference values in adults.

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