Monoclonal gammapathy of renal significance (MGRS) at the current state: terminology, diagnosis and treatment

In this article we discussed the current state of monoclonal gammapathy of renal significance (Monoclonal Gammopathy of Renal Significance MGRS) and revealed problems of B-cell clone secreting nephrotoxic monoclonal immunoglobulin identification. We followed 276 patients with monoclonal gammapathy including patients with non-amyloid nephropathy. The majority of patients had systemic AL-amyloidosis. We established better survival of the treated patients with systemic AL-amyloidosis in comparison with retrospective untreated cohort. We considered current treatment of patients with non-amyloid nephropathy and focused on the crucial role of multidisciplinary approach in management of these patients.

Epidemiology and etiopathogenesis of multiple myeloma and monoclonal gammapathy of undetermined significance

Multiple myeloma (MM) accounts for about 13% of haematological malignancies. Etiopathogenesis is still not fully understood. Confirmed risk factors include the following: age, male sex, black race and MM among first-degree relatives. MM may be preceded by monoclonal gammapathy of undetermined significance (MGUS). The risk of progression is about 1% per year. Genetic changes, proinflammatory and proangiogenic cytokines and some infections may play a role in this risk. With regard to lifestyle risk factors, only obesity and overweight were associated with increased MM incidence and elevated risk for transformation of MGUS to MM. Regarding occupational exposure, there is an increased risk of MM among farmers, firefighters and hairdressers. As far as autoimmune diseases are concerned, only ankylosing spondylitis and pernicious anemia are associated with significantly increased MM risk. Increased risk of MM was also reported in relatives of MM patients, especially in first-degree relatives and in African-American families. The risk of MGUS is elevated in both first-degree relatives of MM and MGUS patients. Data from genetic analysis indicated translocations involving immunoglobulin heavy chain (IGH) loci, hyperphosphorylation of several proteins which are the targets for paraproteins produced by malignant plasma cells and single nucleotide polymorphisms (susceptibility loci) as the potential genetic predisposition to multiple myeloma. The mechanism of heterogeneity of clinical manifestations of MM is not known. Anemia is less frequent in patients whose relatives were diagnosed with hematologic malignancy compared to those with a negative family history. In patients from a younger age group, osteolytic bone lesions were more common than in older patients. In conclusion, environmental exposures modify the genetic predisposition to MM and MGUS.

EVALUATION OF HUMAN IMMUNOGLOBULIN EFFECTIVENESS IN PATIENTS WITH SENSORYMOTOR POLYNEUROPATHY ASSOCIATED WITH MONOCLONAL GAMMAPATHY OF UNDETERMINED SIGNIFICANCE

Introduction. A number of paraproteinemic polyneuropathy is directly linked to the monoclonal gammapathy of undetermined significance (MGUS). One of the first manifestations of MGUS in addition to the secretion of monoclonal immunoglobulin, and long before the manifestation of malignancy is polyneuropathy.Materials and Methods. Were examined in 16 patients with polyneuropathy associated with MGUS in age from 53 to 78 years. Patients underwent a course of infusion therapy with human immunoglobulin in the dose of 0.4 g/kg for 5 days.Results. After treatment revealed a reduction of the manifestations of the sensory component of the neuropathy, neuropathic pain and sensitive ataxia that was confirmed by electromyographic data of stabilography, and a rating on a scale Lovett, the scale of neuropathy disability score, the questionnaire «Pain detect». The motor component of polyneuropathy had more persistent symptoms.Conclusion. Treatment with human immunoglobulin is effective in reduction of neuropathic pain and sensory ataxia and in increase of superficial and deep sensation, while the motor component of polyneuropathy had more persistent symptoms.

Immunoglobulinopathies in patients with angioimmunoblastic T-cell lymphoma

Contex. Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkins lymphoma, characterized by generalized lymphadenopathy, hepatosplenomegaly and dysproteinemia. Hypergammaglobulinaemia is revealed in 50-83% pts with AITL. However, the characteristics of immunoglobulinopathies observed in AITL are scarce. Objective: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease. Patients and methods. 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay. Results. Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2. Conclusions. Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.