Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2617_Библиотеки_им_академика_М_И_Перельмана

Protein diagnostics mainly deals with monoclonal gam­mopathies, conditions characterized by the presence of a monoclonal immunoglobulin (or part of it) in the blood or in the urine. This chapter rst examines the clinical rele­vance of the condition, which ranges from clinically occult forms, represented by monoclonal gammopathy of unde­termined signicance, to forms in which the clinical con­dition is determined by effects due to the peculiar characteristics of monoclonal immunoglobulin, to true neoplasms, such as multiple myeloma. Then the laboratory techniques that allow the management of patients with monoclonal gammopathy are described: protein electro­phoresis (serum and urine), for the detection and quanti­cation of the monoclonal component; immunological typing, for the denition of the class and type of immuno­globulin involved; measurement of serum-free light chains and of the immunoglobulins not involved in monoclonal­ity. In the second part, the other eld of protein diagnostics is introduced, i.e., the measurement of some clinically rel­evant serum proteins. Those taken into consideration are albumin, α1-antitrypsin, haptoglobin, β2-microglobulin, ceruloplasmin, complement, immunoglobulins, C-reactive protein, transthyretin. For each of these, a summary of the physicochemical characteristics and biological function is presented as well as indications for their appropriate clini­cal use.

Among the clinically occult forms, i.e., those conditions in which MG is not associated with clinical manifestations, the most frequently encountered is Monoclonal Gammopathy of Undetermined Signicance (MGUS), a term coined by Robert Kyle in 1978. MGUS is dened as the presence of a MC in serum or urine without clinical evidence of multiple myeloma, AL amyloidosis, Waldenström’s disease, or other related disorders. Epidemiologically, MGUS is far from to be a rare condition, its prevalence increases with age, is higher in males and in Africans and African-Americans than in Caucasians. In an important population-based study in the United States, the prevalence of this condition in the general

2020. MM predominantly affects the elderly population with a mean age at diagnosis of 69 years, while it occurs very rarely under 40years. Myelomatous cells reside in the bone marrow, where they often prevail over other cell types caus­ing typical lytic lesions in bone tissue. In these neoplastic forms with large expanding clones of secreting plasma cells, the clinic is dominated by systemic effects caused by the expansion of the malignant clone, such as anemia, bone lesions, hypercalcemia, renal damage, and infections. Despite the signicant increase in 5-year survival from 25% between 1975 and 1977, to 43% between 2002 and 2008, MM is still considered a poor prognosis disease. In the non­neoplastic forms with small or very small clones, the clinical manifestations may be due to biological effects caused by the biochemical characteristics of the MC.These can range from vasculitis and neuropathy, due to the specic antibody activity of MC, to cardiac or renal functional decit due to the deposition of MC in organs or tissues. Among these, the most frequently encountered pathology is immunoglobulin light-chain amyloidosis (AL amyloidosis), characterized by a plasma cell clone producing light chains with conforma­tional abnormalities that cause systemic proteotoxicity with rapid deterioration of the function of vital organs where amyloid brils are deposited. In this group of diseases, cryo­globulinemias can also be encountered. Cryoglobulins are Ig that invitro precipitate if they are subjected to temperatures below 37 °C, but they redissolve when brought to 37 °C again. In Brouet’s 1974 classication, which remains the most widely used, three types of cryoglobulinemia are dis-

Electrophoretic techniques are at the heart of protein diagnos­tics, as they can detect and characterize serum and urine MCs.

subjected to electrophoresis in the absence and in the pres­ence of antisera (anti-γ, -α, -μ, -κ, -λ). The immunocomplexes that are thus formed migrate in the capillary at a very different

Serum electrophoresis (S-EF) is the test of choice for the detection and quantication of serum MCs, as it is able to detect the molecular homogeneity of the protein. MCs appear as a sharp band in the electrophoretic pattern and can migrate to different areas of the trace; some examples are shown in Fig.12.7. Whichever technique is chosen (AGE or CE), it is important that the employed method shows a high resolution, reaching a sensitivity of <1g/L (1.16) and that the personnel

Any alteration in the electrophoretic pattern (supranumer­ary band, monoclonal peak, morphological alteration) must

qualitative alterations in the morphology of the MC com­pared to the previous ones and to conrm the disappearance of the MC for the denition of the complete response after treatment in MM.It is important that the method adopted for S-IFE has a high resolution and that the personnel in charge of its interpretation are adequately and specically trained. Some examples of typing are presented in Fig.12.8 (panels a–d).