European Journal of Biomedical and Pharmaceutical Sciences

IMMUNOGLOBULINS DETECTION AS BIOLOGICAL MARKERS OF MULTIPLE MYELOMA

Dr. Anil Batta

ABSTRACT

Assessing serum biological markers is an essential component of detecting and monitoring multiple myeloma disease progression. Multiple myeloma is the second most common blood malignancy, and represents approximately 1% of all cancers with a disease burden of approximately 120,000 new cases worldwide per year. Multiple myeloma is typically characterized by the observation of monoclonal plasma cells, the presence of circulating monoclonal protein immunoglobulin, and related organ damage. Protein patterns can be altered in the presence of monoclonal protein (M-spike present), AAT deficiency (reduction in alpha-1 Antitrypsin), as well as nephrotic, acute phase, or inflammatory syndromes, which can result in changes in multiple fractions. Additionally, capillary zone electrophoresis multichannel techniques have been introduced that monitor migration of serum proteins by recording optical absorption at 210 nm in an optical window in the capillary. Measurement of intact Ig’κ, Ig’λ, and Ig’κ/Ig’λ ratio has been made possible with the recent availability of heavy light chain immunoassays (such as The Binding Site’s Heavylite) or the intct Ig subsets: IgGκ, IgGλ and IgAκ and IgAλ, Ig’κ, Ig’λ, and Ig’κ/Ig’λ ratios. These assays utilize epitopes which span specific intact heavy and light chain pairings. The primary reason for performing serum protein electrophoresis is to discover a paraprotein or B cell dyspraxia. An irregularity in the gamma region can be due to a small monoclonal band, free light chains (FLC) or oligoclonal IgG. Other findings of clinical significance include increased alpha-1 and alpha-2 globulins indicative of an acute phase response, a decrease in alpha-1 globulins suggestive of alpha-1 antitrypsin (A1AT) deficiency (that can be followed up with phenotyping to check for a clinically significant A1AT variant), an increase in the beta-1 region suggestive of increased transferrin and iron deficiency, a polyclonal increase in gamma globulins indicative of in inflammation or infection of liver disease. Evidence of organ damage resulting from multiple myeloma clonal plasma cell proliferative disorder includes the CRAB criteria of hypocalcaemia, renal insufficiency, anemia, and bone lesions. The main reason for performing urine protein electrophoresis is to find a light chain myeloma producing an excess of free light chains (Bence Jones protein), an important part of a myeloma screen. A band in the urine protein electropherogram may also result from an intact monoclonal immunoglobulin, especially if the patient has poor renal function. Immunofixation is important in defining the nature of the band and in distinguishing between Bence Jones protein and an intact monoclonal protein originating from the serum. From the urine electropherogram we can also tell if the proteinuria is of glomerular origin with a predominance of albumin, or if it has tubular components with excretion of smaller molecular weight proteins such as retinol binding protein and alpha-1 microglobulin. Fragmented albumin in urine is occasionally seen but is of unknown significance.6 Historically, urine has been concentrated by either removal of water from the specimen leaving the proteins in higher concentration, or by centrifugation whereby the proteins are spun away from the majority of the water.

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