The term monoclonal gammopathy (GM) refers to a clinical condition determined by the presence in a patient's serum and urine of evident amounts of monoclonal type immunoglobulin chains (CM), caused by the proliferation of a single clone of B cells. An increase in monoclonal component immunoglobulins is the result of a process of reproduction of a single plasma cell, with malignant or potentially malignant character, while a polyclonal increase is caused by reactive or inflammatory processes. Monoclonal gammopathies can be classified according to their clinical manifestations: clear clinical examples caused by the proliferation of neoplastic plasma cells can be multiple myeloma, Waldenstrom macroglobulinemia, amyloidosis, micromyeloma and Bence Jones proteinuria. Transient monoclonal gammopathies, on the other hand, may be associated with drug hypersensitivity, viral infections, microbial infections and active viral and chronic hepatitis. On the other hand, gammopathies of uncertain significance (MGUS) are often caused by chronic inflammation (rheumatoid arthritis, chronic biliary infections, etc.), AIDS, non-reticular neoplasms such as intestinal tumors, biliary tract tumors, etc. The method of choice used to diagnose the presence of a monoclonal gammopathy is the electrophoresis of seroproteins, a test that allows to detect the presence of serum CM and to quantify them with the capillary method and on agarose gel. Abnormal peaks in serum and urine electrophoresis, particularly in Beta 2 and gamma zones, are always considered probable monoclonal proteins and therefore an indication of monoclonal gammopathy. It is therefore necessary to carry out a second level test in order to confirm and eventually typify serum CM: immunofixation on agarose gel (IFE). After detecting and typing the CM, the clinician usually requires urinary immunofixation for the detection of Bence Jones proteinuria which, if present, compares with serum immunofixation in order to confirm the identity of free monoclonal light chains. This thesis work was based on the evaluation of the analytical characteristics and on the comparison of the data obtained from the electrophoresis requests of the seroproteins carried out in internal and external patients of the Hospital of the Province of Pavia, Voghera Hospital Presidium, Department of Clinical Pathology, Laboratory Medical Service, in a period between March 1, 2019 and July 31, 2019. The following thesis work has shown (as confirmed by the literature), in terms of typing, a significant share of IgG (47.6%) as the main monoclonal proteins. Less frequently, IgM components (14.7%), IgA (9.7%), biclonality (9.3%) and nondosable CM (9.8%) were found. On the other hand, trichlonality (0.8%), the presence of free light chains in serum (0.4%), free light monoclonal chains in association with one or more monoclonal components (0.5%), monoclonal components that in the past were present but at the current immunofixation are regressed (1.4%) and oligocloniality (1.2%) are much rarer. The negative ones represent 4.5%. Moreover, it is very evident that the proliferative pathologies of one or more plasma cellular clones involve more older people or, in any case, patients over 50 years of age.
Con il termine di gammopatia monoclonale (GM) si intende una condizione clinica determinata dalla presenza nel siero e nelle urine di un paziente di evidenti quantità di catene immunoglobuliniche di tipo monoclonale (CM), causata dalla proliferazione di un singolo clone di cellule B. Un incremento delle immunoglobuline a componente monoclonale è il risultato di un processo di riproduzione di una singola plasmacellula, con carattere maligno o potenzialmente tale, mentre un incremento policlonale è causato da processi reattivi o infiammatori. Le gammopatie monoclonali possono essere classificate in base alle loro manifestazioni cliniche: chiari esempi clinici causati dalla proliferazione di plasmacellule neoplastiche possono essere il mieloma multiplo, macroglobulinemia di Waldenstrom, amiloidosi, micromieloma e proteinuria di Bence Jones. Le gammopatie monoclonali transienti, invece, possono essere associate a ipersensibilità ai farmaci, infezioni virali, infezioni microbiche ed epatiti virali e croniche attive. Invece, spesso, le gammopatie di significato incerto (MGUS) sono causate da infiammazioni croniche (artrite reumatoide, infezioni croniche biliari, etc), AIDS, neoplasie non reticolari come tumori intestinali, del tratto biliare etc. Il metodo di elezione utilizzato per diagnosticare la presenza di una gammopatia monoclonale è lelettroforesi delle sieroproteine, un test che permette di rilevare la presenza di CM sieriche e di quantificarle sia con il metodo capillare che su gel di agarosio. Picchi anomali nei quadri elettroforetici di siero e urine, in particolare nelle zone Beta 2 e gamma, sono sempre considerate probabili proteine monoclonali e pertanto un indizio di gammopatia monoclonale. È quindi necessario approfondire con un test di secondo livello per poter confermare ed eventualmente tipizzare la CM sierica: limmunofissazione su gel di agarosio (IFE). Dopo aver rilevato e tipizzato la CM, il clinico solitamente richiede limmunofissazione urinaria per la ricerca della proteinuria di Bence Jones la quale, se presente si confronta con limmunofissazione sierica, al fine di confermare lidentità stessa delle catene leggere libere monoclonali. Questo lavoro di tesi si è basato sulla valutazione delle caratteristiche analitiche e sulla comparazione dei dati ottenuti dalle richieste di elettroforesi delle sieroproteine effettuate a pazienti interni ed esterni dellAzienda Ospedaliera della Provincia di Pavia, Presidio Ospedaliero di Voghera, Dipartimento di Patologia Clinica, Servizio Medicina di Laboratorio, in un periodo compreso tra il primo marzo 2019 e il 31 luglio 2019. Dal seguente lavoro di tesi è risultato (come confermato anche dalla letteratura), in termini di tipizzazione, una quota importante di IgG (47,6%) come principali proteine monoclonali. Meno frequentemente si sono evidenziate componenti IgM (14,7%), IgA (9,7%), biclonalità (9,3%) e CM non dosabili (9,8%). Risultano invece molto più rare le triclonalità (0,8%), la presenza di catene leggere libere nel siero (0,4%), catene leggere monoclonali libere in associazione ad una o più componenti monoclonali (0,5%), componenti monoclonali che in passato erano presenti ma allattuale immunofissazione risultano essere regredite (1,4%) e le oligoclonalità (1,2%). Quelle risultate negative rappresentano il 4,5%. Inoltre, risulta essere molto evidente come le patologie proliferative di uno o più cloni plasmacellulari coinvolgano maggiormente le persone più anziane, o comunque pazienti con età superiore ai 50 anni.
Gammopatie Monoclonali: metodologie e diagnosi di 984 casi nel presidio ospedaliero di Voghera
PASQUALINI, SONIA
2018/2019
Abstract
The term monoclonal gammopathy (GM) refers to a clinical condition determined by the presence in a patient's serum and urine of evident amounts of monoclonal type immunoglobulin chains (CM), caused by the proliferation of a single clone of B cells. An increase in monoclonal component immunoglobulins is the result of a process of reproduction of a single plasma cell, with malignant or potentially malignant character, while a polyclonal increase is caused by reactive or inflammatory processes. Monoclonal gammopathies can be classified according to their clinical manifestations: clear clinical examples caused by the proliferation of neoplastic plasma cells can be multiple myeloma, Waldenstrom macroglobulinemia, amyloidosis, micromyeloma and Bence Jones proteinuria. Transient monoclonal gammopathies, on the other hand, may be associated with drug hypersensitivity, viral infections, microbial infections and active viral and chronic hepatitis. On the other hand, gammopathies of uncertain significance (MGUS) are often caused by chronic inflammation (rheumatoid arthritis, chronic biliary infections, etc.), AIDS, non-reticular neoplasms such as intestinal tumors, biliary tract tumors, etc. The method of choice used to diagnose the presence of a monoclonal gammopathy is the electrophoresis of seroproteins, a test that allows to detect the presence of serum CM and to quantify them with the capillary method and on agarose gel. Abnormal peaks in serum and urine electrophoresis, particularly in Beta 2 and gamma zones, are always considered probable monoclonal proteins and therefore an indication of monoclonal gammopathy. It is therefore necessary to carry out a second level test in order to confirm and eventually typify serum CM: immunofixation on agarose gel (IFE). After detecting and typing the CM, the clinician usually requires urinary immunofixation for the detection of Bence Jones proteinuria which, if present, compares with serum immunofixation in order to confirm the identity of free monoclonal light chains. This thesis work was based on the evaluation of the analytical characteristics and on the comparison of the data obtained from the electrophoresis requests of the seroproteins carried out in internal and external patients of the Hospital of the Province of Pavia, Voghera Hospital Presidium, Department of Clinical Pathology, Laboratory Medical Service, in a period between March 1, 2019 and July 31, 2019. The following thesis work has shown (as confirmed by the literature), in terms of typing, a significant share of IgG (47.6%) as the main monoclonal proteins. Less frequently, IgM components (14.7%), IgA (9.7%), biclonality (9.3%) and nondosable CM (9.8%) were found. On the other hand, trichlonality (0.8%), the presence of free light chains in serum (0.4%), free light monoclonal chains in association with one or more monoclonal components (0.5%), monoclonal components that in the past were present but at the current immunofixation are regressed (1.4%) and oligocloniality (1.2%) are much rarer. The negative ones represent 4.5%. Moreover, it is very evident that the proliferative pathologies of one or more plasma cellular clones involve more older people or, in any case, patients over 50 years of age.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/17694