Laboratory and clinical features of abnormal macroenzymes found in human sera

Abstract

We report the analysis of unusual macroenzymes, performed in our laboratory, and review the relevant literature. In particular, we focused on macro AST, macroamylase, macro LD and macro CK. Macroenzymes are seen in healthy subjects, but can also be related to disease; thus, accurate detection is useful in day-to-day clinical practice. The macroenzyme is thought to be a specific antigen–antibody complex from the following findings: (1) the complex could be dissociated under acidic pH levels; (2) binding specificity of immunoglobulin in the complex was observed; (3) the binding site of immunoglobulin in the complex was Fab portion; and (4) the maternal IgG involved with macroenzyme was transferred to her children. This article is part of a Special Issue entitled: Medical Proteomics

Macro Creatine Kinase (macro CK) in Clinical Practice

“…CK catalyzes the reversible transformation of ATP + creatine in ADP and phosphocreatine [1,3]. CK is a dimeric globular protein of 43 kDa who expresses different isozymes that could be classified according to the combination of component subunits or according intracellular expression [1][2][3][4]. CK has two possible subunits: type M -muscular and type B -brain and the combination of two identical or different subunits leads to three isozymes of CK: CK -MM found mainly in the skeletal muscle, CK -BB found mainly in the brain and in other visceral tissues, CK -MB found mainly in the cardiac muscle and in in small quantities in the skeletal muscle [1][2][3][4].…”

“…CK is a dimeric globular protein of 43 kDa who expresses different isozymes that could be classified according to the combination of component subunits or according intracellular expression [1][2][3][4]. CK has two possible subunits: type M -muscular and type B -brain and the combination of two identical or different subunits leads to three isozymes of CK: CK -MM found mainly in the skeletal muscle, CK -BB found mainly in the brain and in other visceral tissues, CK -MB found mainly in the cardiac muscle and in in small quantities in the skeletal muscle [1][2][3][4]. According to the intracellular expression there are five isozymes of CK: three cytosolic -the muscular isoforms expressed in the skeletal (CK -MM) and cardiac muscle (CK -MB) and the ubiquitous brain isoform expressed in the brain and in non-muscular tissue (CK-BB) -and two mitochondrial -the muscle specific (sarcomeric) and the ubiquitous form (non-sarcomeric) [2][3][4].…”

“…An important cause for false, persistently elevated levels of CK and/or CK -MB is the apparition of macroCK. If normal CK is a globular dimeric protein with molecular weight of 43 kDa, macroCK is an octameric protein that is a complex formed by CK -MM and CK -MB with a immunoglobulin (Ig) usually Ig G with a kappa light chain, but sometimes Ig A or Ig M -type I of macroCK (molecular weight >200 kDa) or a polymer of mitochondrial CK -type II of macroCK (molecular weight >300 kDa) [3,4,9,[26][27][28]. The electrophoretic separation using agarose gel is useful for detecting normal CK and macroCK and immunofixation with antisera against Ig G is used for type I macroCK [3,22,[26][27][28][29][30].…”

“…The electrophoretic separation using agarose gel is useful for detecting normal CK and macroCK and immunofixation with antisera against Ig G is used for type I macroCK [3,22,[26][27][28][29][30]. Type I of macroCK is migrating between CK -MM and CK -MB (anodal type of macroCK) and type II of macroCK is migrating cathodic to CK -MM (cathodal type of macroCK) [4,22,[26][27][28][29][30]. Two other methods were proposed for the detection of macroCK and other macro enzymes: polyethylene glycol (PEG) precipitation and ultrafiltration [31,32].…”

“…Two other methods were proposed for the detection of macroCK and other macro enzymes: polyethylene glycol (PEG) precipitation and ultrafiltration [31,32]. Sometimes, patients with type I macroCK have false high levels of CK -MB, with an increase ratio of CK -MB/total CK or even CK -MB level higher than the total level of CK, that mimics a myocardial lesion as the acute coronary syndrome and testing troponins levels is recommend to clarify this type of situations with major clinical consequences [4,[26][27][28][29]. There are reports about macroCK in multiple members of a family, possible by transplacentar transfer of Ig G against CK from mother to the child [4,25].…”