Monoclonal Ig is detected in three main circumstances: the patient has symptoms of the underlying disease (e.g. bone-related signs of myeloma); the patient has renal or other complications caused by the protein itself; or, increasingly often, it is an incidental finding in a screening test. Incidental detection is mainly through a raised erythrocyte sedimentation rate (ESR), which is then investigated further by serum protein electrophoresis to distinguish between the possible causes: an « inflammatory » syndrome (accompanied by elevated levels of alpha2 globulin, CRP and fibrin), general elevation of serum Igs (polyclonal hypergammaglobulinaemia), or elevation of just one Ig (monoclonal Ig).
Monoclonal Ig can be observed during some infectious diseases and in primary or acquired immunodeficiencies or immunocompromised states. Infections associated with monoclonal Igs include bacterial infections (endocarditis, osteomyelitis) and parasitic infections, but mostly viral infections, the main viruses responsible being human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Monoclonal Ig is a common complication in patients taking immunosuppressants following organ or bone marrow transplantation. In common with the monoclonal Igs associated with other immunodeficiencies or infections, the clinical course of those encountered in transplant recipients is variable: they may remain stable, precede haematological disease, and sometimes, remarkably, resolve spontaneously, usually as the associated infection and/or immunodeficiency improves.
Once a monoclonal Ig is detected, regardless of the circumstances, the workup involves three stages:
1) The monoclonal Ig is diagnosed, characterized and quantified through laboratory investigations. Serum protein electrophoresis will usually establish the presence of monoclonal Ig and indicate the quantity present and whether the levels of other (« polyclonal ») Igs are reduced. It is particularly important to analyse urinary proteins (essentially through urine protein testing and electrophoresis) when investigating an apparently isolated decrease in gammaglobulins, as this anomaly is almost always present in myelomas that secrete only light chains.
2) The investigations used to detect overt proliferative disease and any resulting complications depend on the type of monoclonal Ig involved. For monoclonal IgM, the main diagnosis will be Waldenström’s macroglobulinaemia, so the presence of lymph node enlargement and abnormal cells in the bone marrow will be investigated. If the monoclonal Ig is IgG, IgA or light chains only, the main problem is to determine whether myeloma is present.
3) Some complications related to the presence of the monoclonal Ig in serum and/or urine occur regardless of whether the monoclonal Ig is accompanied by detectable abnormal cell proliferation. These complications are therefore investigated independently of the previous step.