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Immunoglobulin variable region heavy chain (IgVH) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-time reverse transcription-polymerase chain reaction (RT-PCR). The features of activation-induced cytidine deaminase (AID) protein and mRNA transcripts were explored in liver tissue biopsies and portal tracts isolated using laser capture microdissection. In chronically HCV-infected patients, AID mRNA expression was almost threefold higher in those with than in those without CV and sevenfold higher than in healthy subjects (median-fold: 6·68 versus 2·54, P = 0·03 and versus 0·95, P = 0·0003). AID transcript levels were significantly higher in polyclonal than in clonally restricted B cell preparations in either CV or non-CV patients (median-fold, 15·0 versus 2·70, P = 0·009 and 3·46 versus 1·58, P = 0·02, respectively). AID gene expression was found to be related negatively to age and virological parameters. AID protein was found in portal tracts containing inflammatory cells that, in several instances, expressed AID mRNA transcripts. Our data indicate that the aberrant expression of AID may reflect continuous B cell activation and sustained survival signals in HCV-related CV patients. [ABSTRACT FROM AUTHOR]

Imbalance of cytokine homeostasis is a prominent feature of both experimental and human systemic lupus erythematosus (SLE). Because interleukin (IL)-12 promotes interferon (IFN)-γ production leading to polarization of peripheral cells toward a T helper (Th) 1 phenotype, we investigated its role in lupus nephritis (LN). Soluble Th1 and Th2 cytokines were measured by enzyme-linked immunosorbent assay (ELISA) in sera and urines of SLE patients and controls. Th1/Th2 peripheral lymphocyte polarization was determined by flow cytometry. Glomerular accumulation of IL-12 was evaluated by immunohistochemistry, whereas urinary IL-12 was evaluated by ELISA. Higher serum IL-12 levels in SLE were associated with LN, whereas IL-4 was unrelated to the renal damage. Peripheral cells from LN patients showed a Th1 phenotype with a high IFN-γ expression that paralleled the severity of renal damage. IL-12 was present within glomerular mononuclear cells in classes IV and V LN, and its accumulation was correlated strongly with urinary levels. IL-12 overexpression in SLE may contribute to the development of LN. Both serum and urinary IL-12 elevation reflect its glomerular production and parallel Th1 polarization of peripheral T cells and high IFN-γ production. In SLE patients, IL-12 measurement may thus be predictive of the development of LN. [ABSTRACT FROM AUTHOR]

The relationship between the occurrence of cryoglobulins and hepatitis C virus (HCV) productive infection in peripheral blood and bone marrow-derived lymphocytes was explored. HCV minus strand RNA, the viral replicative intermediate, was searched for by a polyA+ tract strand-specific Tth-based reverse transcriptase–polymerase chain reaction (RT–PCR) in lymphoid cells of 46 patients with acute and chronic infection. The HCV minus strand was demonstrated in RNA extracted from six (13%) and five (11%) peripheral blood and bone marrow-derived lymphocytes, respectively. The HCV replicating form in lymphoid cells was associated strictly with mixed cryoglobulinaemia (MCG), in that it was found in six of 13 (46%) MCG patients, including two with B cell non-Hodgkin's lymphoma (NHL). No traces of HCV-negative strand RNA were found in four patients with acute hepatitis C, in 15 with chronic active hepatitis without extrahepatic disorders, in seven with monoclonal gammopathy of undetermined significance, and in seven with B-NHL without MCG. These results emphasize the direct role of the virus in the pathogenesis of MCG and support the contention that HCV is not specifically lymphotropic, its entry and replication in lymphoid cells being determined largely by selective interactions. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the role of interleukin (IL)-18 in patients with inflammatory myopathies (IM) such as dermatomyositis (DM) and polymyositis (PM) in relation to the possible predominance of a Th1 immune response in their pathogenesis. Serum concentrations of IL-18, interferon (IFN)-γ, IL-4 and IL-6 were measured in six patients by enzyme-linked immunosorbent assay (ELISA). IL-18 expression was evaluated by in situ hybridization (ISH), whereas CD68, CD8 and CD83 were investigated by immunohistochemistry (IHC) to define the main producers of IL-18. Lastly, the expression of both IL-18 receptor (IL-18R) and monocyte chemoattractant protein (MCP)-1 was also explored by IHC. High serum levels of IL-18 and IFN-γ, and conversely low titres of IL-4 and IL-6, were demonstrated in both diseases. In addition, IL-18 was overexpressed in muscle biopsy specimens from patients with IM. Both macrophages and dendritic cells (DC) surrounding either perivascular and perimysium areas in DM or endomysium in PM were the main producers of IL-18. Endothelial cells (EC), smooth muscle cells (SMC) and CD8+ T cells expressed a high content of IL-18R. Vessel cells overexpressed MCP-1 in parallel with IL-18R. High concentrations of serum IL-18 as well as muscular up-regulation of IL-18 and IL-18R suggest that deregulation of the IL-18/IL-18R pathway is a pathogenetic mechanism in IM. Measurement of IL-18 may thus predict the severity of both DM and PM. [ABSTRACT FROM AUTHOR]

In clinical and pathological terms hepatitis C virus (HCV)-infected patients can be subdivided into two main groups with and without mixed cryoglobulinaemia (MC). Involvement of blood mononuclear cells by HCV has potentially important implications. To this end, HCV-RNA levels in peripheral blood lymphocytes (PBL) preparations of 20 chronically HCV-infected patients with MC were measured and compared with those found in a group of 20 patients without MC matched for age, serum HCV-RNA, infectious genotype, source and presumable duration of infection. Phenotypic abnormalities of PBL subsets in each group of patients were determined by cell surface marker expression and compared. Results showed a significant enrichment of HCV-RNA in PBL of MC patients compared with a non-MC group ( P = 0·01). Different distribution of HCV-RNA was accompanied by evidence of an increased frequency of circulating B cells. These data indicate that MC patients are characterized distinctly by a higher quota of cell-associated viral load. [ABSTRACT FROM AUTHOR]

The role of hepatits C virus (HCV) in the production of renal injury has been extensively investigated, though with conflicting results. Laser capture microdissection (LCM) was performed to isolate and collect glomeruli and tubules from 20 consecutive chronically HCV-infected patients, namely 6 with membranoproliferative glomerulonephritis, 4 with membranous glomerulonephritis, 7 with focal segmental glomerulosclerosis and 3 with IgA-nephropathy. RNA for amplification of specific viral sequences was provided by terminal continuation methodology and compared with the expression profile of HCV core protein. For each case two glomeruli and two tubular structures were microdissected and processed. HCV RNA sequences were demonstrated in 26 (65%) of 40 glomeruli, but in only 4 (10%) of the tubules (P < 0·05). HCV core protein was concomitant with viral sequences in the glomeruli and present in 31 of the 40 tubules. HCV RNA and/or HCV core protein was found in all four disease types. The immunohistochemical picture of HCV core protein was compared with the LCM-based immunoassays of the adjacent tissue sections. Immune deposits were detected in 7 (44%) of 16 biopsy samples shown to be positive by extraction methods. The present study indicates that LCM is a reliable method for measuring both HCV RNA genomic sequences and HCV core protein in kidney functional structures from chronically HCV-infected patients with different glomerulopathies and provides a useful baseline estimate to define the role of HCV in the production of renal injury. The different distribution of HCV RNA and HCV-related proteins may reflect a peculiar‘affinity’ of kidney microenvironments for HCV and point to distinct pathways of HCV-related damage in glomeruli and tubules. [ABSTRACT FROM AUTHOR]

SUMMARY Hepatitis C virus (HCV) infection has been detected in a large proportion of patients with mixed cryoglobulinaemia (MC). Circulating ‘free’ non-enveloped HCV core protein has been demonstrated in HCV-infected patients, and this suggests its possible involvement in the formation of cryoprecipitable immune complexes (ICs). Thirty-two anti-HCV, HCV RNA-positive patients with type II MC were evaluated. Non-enveloped HCV core protein, HCV RNA sequences, total IgM, rheumatoid factor (RF) activity, IgG and IgG subclasses, C3 and C4 fractions, C1q protein and C1q binding activity were assessed in both cryoprecipitates and supernatants. Non-enveloped HCV core protein was demonstrated in 30 of 32 (93·7%) type II MC patients. After separation of cold-precipitable material, the protein was removed completely from supernatant in 12 patients (40%), whereas it was enriched in the cryoprecipitates of the remaining 18. In addition, HCV RNA and IgM molecules with RF activity were concentrated selectively in the cryoprecipitates. Differential precipitation was found for both total IgG and IgG subclasses, as they were less represented in the cryoglobulins and no selective enrichment was noted. Immunological characterization of HCV core protein-containing cryoprecipitating ICs after chromatographic fractionation showed that the IgM monoclonal component had RF activity, whereas anti-HCV core reactivity was confined to the IgG fraction. C1q enrichment in addition to high avidity of ICs for C1q binding in the cryoprecipitates suggest that complement activation may occur through the C1q protein pathway. The present data demonstrate that non-enveloped HCV core protein is a constitutive component of cryoprecipitable ICs in type II MC patients. [ABSTRACT FROM AUTHOR]

Intracellular cytokine production by peripheral blood mononuclear cells (PBMC) was analysed in 51 patients with multiple myeloma (MM), 22 with monoclonal gammopathy of undetermined significance (MGUS) and 20 healthy subjects, as a parameter of immunological dysfunction in MM. An increased proportion of T cells and HLA-DR+ cells producing IL-6 was observed in MM patients with active disease (at diagnosis and relapsing) compared with patients in remission and with MGUS, whereas no difference of IFN-γ+, IL-2+ PBMC between patients and controls was evident. Determination of serum cytokine levels demonstrated that the imbalanced IL-6 production by T cells and the defective anti-tumour Th1 cell activity were related to elevated levels of IL-6 and IL-12. In vitro studies of PHA- and anti-CD3/anti-CD28 MoAbs stimulation of PBMC demonstrated the ability of lymphocytes from MM patients to differentiate towards the Th1 subset in the presence of rIL-12. By contrast, addition of exogenous rIL-6 impaired IFN-γ production by rIL-12-prompted T cells. Inhibition of Th1 polarization of the immune response by IL-6 was direct on T cells and not mediated by dendritic cells (DC). Evaluation of the ability of MM-derived DC to stimulate cell proliferation of allogenic T lymphocytes and produce IL-12 in vitro, in fact, suggested that MM-derived DC were functionally active. Taken as a whole, these results indicate that a deregulated cytokine network occurs in active MM. They also suggest that increased IL-6 production by peripheral T lymphocytes contributes to the immune dysfunction observed in MM, and enables tumour cells to escape immune surveillance by preventing the anti-tumour Th1 immune response. [ABSTRACT FROM AUTHOR]

The reverse haemolytic plaque assay (RHPA) was used to enumerate circulating and bone marrow (BM) immunoglobulin secreting cells (ISC) in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), as well as in normal controls. Significantly greater quantities of plaque forming cells (PFC) secreting the same isotype of the serum M component were detected in the peripheral blood of MM patients than in the blood of MGUS patients or normal subjects. Comparative analysis of the numbers of monoclonal PFC in both peripheral blood (PB) and BM at diagnosis usually showed a higher number as well as more precocious chemotherapy-induced variations of ISC in the BM compartment than in the PB. Although large individual variations were observed during follow-up studies of MM patients, persistently increased or decreased levels of monoclonal PFC were often found to accompany (and sometimes to precede by months) the phases of relapse or remission, respectively. Similarly to IgG-MGUS patients, a distorted ratio of IgGκ to IgGλ secreting cells was consistently detected in patients with smouldering MM, although the total number (IgGκ plus IgGλ) of ISC appeared within normal limits. It is suggested that, in addition to other clinical and laboratory criteria, the RHPA may be of value in the diagnosis and follow-up of patients with monoclonal gammopathies. [ABSTRACT FROM AUTHOR]

The chemotactic responsiveness of peripheral blood monocytes was evaluated in three groups of subjects: 32 patients with multiple myeloma, 27 subjects with benign monoclonal gammapathy, and 64 normal controls. Monocyte chemotactic responsiveness was significantly depressed both in multiple myeloma patients (P<0.001) and in subjects with benign monoclonal gammapathy (P<0.001) as compared to that found in the control population. Although the results of chemotactic response obtained in multiple myeloma and in benign monoclonal gammapathy patients were largely overlapping, a significant difference was also found between the mean values of the two groups (P<0.025). The results support the hypothesis that myelomatosis, similarly to other neoplasms, may affect monocyte migratory activity thus hindering immunologically mediated destruction of tumour cells. [ABSTRACT FROM AUTHOR]

The prevalence of HCV antibodies was determined by a second-generation FLISA and a four-antigen recombinant immunoblot assay in nine intravenous immunoglobulin (IVIG) preparations commercially available in Italy. In addition, the clinical safety of six of them was ascertained by polymerase chain reaction (PCR) of HCV RNA and a prospective study in 14 patients with immunodeficiency disorders. Results indicated that all IVIG preparations were anti-HCV-positive. However, there were substantial variations in their anti-HCV antibody titres. The preparations retained IgG subclass reactivities to HCV-associated structural (C22-3) and non-structural (C33c, C100-3) proteins. Our sensitive and specific PCR assay was unable to detect HCV RNA in the six preparations tested. Clinical surveillance of IVIG-treated patients prospectively evaluated over a mean period of 8 3 months failed to detect clinical and/or biochemical evidence of hepatitis. [ABSTRACT FROM AUTHOR]

Although essential mixed cryoglobulinaemia (EMC) is recognized to be frequently associated with chronic liver disease, aetiology and pathogenesis of liver damage remain unsolved questions. The purpose of this study was to assess the possible causative role of hepalitis C virus (HCV) in the liver impairment occurring in patients with EMC. Twenty-six consecutive EMC patients were evaluated. All patients underwent percutaneous liver biopsy. Anti-HCV antibodies were assayed by ELISA and supported by a recombinant immunoblotting assay (4-RIBA). The prevalence of anti-HCV antibodies in patients with and without chronic active liver disease (CALD) was compared. Anti- HCV antibodies were detected in 13 patients (50%) by EUSA and confirmed in II of them (42.3%) by 4-RIBA. the remaining two patients being indeterminate in the supportive assay. CALD correlated significantly with anti-HCV antibodies: indeed. 7/11 (63.6%) anti-HCV- patients showed histological and clinical pictures of CALD. compared with 1/15 (6.6%) anti-HCV patients (P <0.01). With the exception of the patient who was found to be HbsAg+ no liver tissue expressed hepatitis B virus-related antigens in the hepalocytes. Additional histological findings included discrete lymphoid aggregates in portal tracts, siderosis, fatty changes, hyperplasia of Kupffer cells. It can be concluded that chronic liver damage in EMC is frequently associated with anti-HCV antibodies. Although the cause of EMC remains unknown, this study has obvious implications for clarifying the etiology of associated CALD and further supports the therapeutic use of interferons in this disease.Although essential mixed cryoglobulinaemia (EMC) is recognized to be frequently associated with chronic liver disease, aetiology and pathogenesis of liver damage remain unsolved questions. The purpose of this study was to assess the possible causative role of hepalitis C virus (HCV) in the liver impairment occurring in patients with EMC. Twenty-six consecutive EMC patients were evaluated. All patients underwent percutaneous liver biopsy. Anti-HCV antibodies were assayed by ELISA and supported by a recombinant immunoblotting assay (4-RIBA). The prevalence of anti-HCV antibodies in patients with and without chronic active liver disease (CALD) was compared. Anti- HCV antibodies were detected in 13 patients (50%) by EUSA and confirmed in II of them (42.3%) by 4-RIBA. the remaining two patients being indeterminate in the supportive assay. CALD correlated significantly with anti-HCV antibodies: indeed. 7/11 (63.6%) anti-HCV- patients showed histological and clinical pictures of CALD. compared with 1/15 (6.6%) anti-HCV patients (P <0.01). With the exception of the patient who was found to be HbsAg+ no liver tissue expressed hepatitis B virus-related antigens in the hepalocytes. Additional histological findings included discrete lymphoid aggregates in portal tracts, siderosis, fatty changes, hyperplasia of Kupffer cells. It can be concluded that chronic liver damage in EMC is frequently associated with anti-HCV antibodies. Although the cause of EMC remains unknown, this study has obvious implications for clarifying the etiology of associated CALD and further supports the therapeutic use of interferons in this disease. [ABSTRACT FROM AUTHOR]

It has been previously reported that CH1 Fab protein G-contact site is responsible for the widespread recognition of mouse and human IgG Fab by PG. Here we present evidence that PG binding to F(ab′)2 is restricted, as indicated by the lack of reactivity with PG-Sepharose columns of a portion of F(ab′)2 fragments obtained by pepsin digestion of human IgG from a commercial immunoglobulin preparation for intravenous use or purified from sera of two healthy blood donors and two patients with polyclonal hypergammaglobuinaemia. Isoelectric focusing showed that F(ab′)2 fragments that did not bind PG focused in a lower pH range compared with those which did. Testing of the Fab fractions with MoAbs to κ and λ light chains or to γ1, γ2 and γ3-Fab subclass determinants showed that γ2-F(ab′)2 were mainly found in the PG non-reactive F(ab′)2 fraction, and that this distribution was not influenced by the L chain isotype. These results indicate that the PG-specific binding determinant(s) is not expressed in the F(ab′)2 region of most human IgG2. [ABSTRACT FROM AUTHOR]

The authors have recently shown that antibodies with anti-idiotype (Id) specificity to pathogenic Ids of lupus nephritis may occasionally occur in several intravenous immune globulin (IVIG) preparations because they are present in healthy donors and the healthy relatives of SLE patients. in the present study, the authors purified these anti-Ids and treated two SLE patients with nephritis in parallel with conventional high-dose IVIG management with a commercial preparation (IVIG 6) in three controls for two months. Because pathogenic Ids of anti-DNA molecules, such as both 8.12 and F4 Ids, show a cationic mobility in isoelectric focusing, a commercial preparation of IVIG (11) was absorbed on a Sepharose column coupled with DC-305-39 myeloma protein, namely a 8.12+ and F4+ cationic IgG. Infusion of the eluate (EL-11) induced a prompt resolution of proteinuria levels and an evident decrease of serum levels of anti-DNA antibodies in both patients, whereas in the three controls, proteinuria and anti-DNA antibodies were scarcely reduced. In addition, plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were also significantly influenced by both treatments. The mean values of both cytokines increased significantly after 1 h and then progressively declined over the next 48 h. It was of interest, however, that the increased TNF-α in the two EL-11-treated patients was significantly lower than in the three controls. The data suggest that reduction of active lupus nephritis by enriched specific anti-Id molecules is the result of two (or perhaps more) mechanisms: suppression of pathogenic idiotypes at the cellular level and improvement in the mesangium of the secretion of anti-inflammatory cytokines, such as IL-6, whose defective function is related to the autoimmune disorder. [ABSTRACT FROM AUTHOR]

Immunofluorescence (IF) to detect HCV antigens and non-isotopic in situ hybridization (NISH) to detect HCV RNA genome were carried out on bone marrow (BM) and peripheral blood (PB) mononuclear cells (MC) of 11 chronically HCV-infected patients. In four patients (36.4%) HCV antigens were detected in monocytes/macrophages as well as in B lymphocytes in both BMMC and PBMC. Positive T lymphocytes in BMMC were found in three of them, but only one patient showed positive T cells in PBMC. NISH invariably demonstrated minus and plus HCV RNA genomic strands either in monocytes, macrophages or B and T lymphocytes in BMMC and PBMC in the four HCV antigen-positive patients and in two further patients not expressing viral proteins in blood MC. IF signals appeared diffusely distributed within the cytoplasm, or as brilliant granules in distinct submembrane areas or else in cytoplasm membrane. Nuclei never stained. Similarly, NISH displayed HCV RNA accumulation restricted to MC cytoplasm only, nuclei being persistently negative, NISH. however, was unable to detect cell membrane signal. Infection of blood MC is a common event in naturally acquired HCV infection, since none of these patients was conditioned by immunomodulating or immunosuppressive therapies. No difference was found in terms of mean age, length of disease, anti-HCV immune response, type and severity of chronic liver damage between patients with HCV-infected MC and patients without cell infection. These results demonstrate that HCV can infect BMMC and PBMC that represent important extrahepatic sites of virus replication, and may help lo explain the immunological abnormalities observed in chronic HCV carriers. [ABSTRACT FROM AUTHOR]

Soluble CD4 antigen (sCD4) was measured in seven commercially available intravetious immunoglobulin preparations (IVIg) by means of a double determinant immunoassay (DDIA), whereby two MoAbs recognizing two distinct and spatially distant epitopes on CD4 were used to capture and detect the antigen, respectively. Preincubation of six out of seven IVIg, which were found to be apparently positive for sCD4, with mouse- and bovine-derived serum or purified immunoglobulins completely neutralized DDIA reactivity for sCD4. The inhibition was specific since it was not or only partially observed when IVIg were mixed with whole serum or purified IgG from rabbit. Extensive absorption of six IVIg on insolubilized mouse IgG (mIgG) resulted in a complete loss of reactivity. Eluted human anti-mouse antibodies (HAMA) from any ofthe IVIg displayed a dose-dependent binding in a DDIA, though its extent varied from one preparation to another. Western blot analysis showed that HAMA from all IVIg contained no component with a molecular weight identical with or close to that of recombinant CD4. Purified mIgG markedly influenced the sCD4 reactivity of two IVIg (Sandoglobulin and Globuman I.V.) when sCD4 was measured with a purchased 'CD4-specific Test Kit', thus suggesting that HAMA can exceed the absorbing capacity of the sample diluent. Taken as a whole, these data indicate that sCD4-based DDIA signal is mostly, if not completely, generated by the presence of human immunoglobulin with anti-mouse immunogobulin reactivity, thus casting doubts on the actual occurrence of sCD4 in IVIg. [ABSTRACT FROM AUTHOR]

This study was addressed to explore the reactivity of natural anti-idiotypes from commercial lots of immunoglobulins to several idiotypes (lds), usually expressed by anti-DNA molecules in Lupus nephritis. Eleven intravenous immunoglobulin (IVIG) preparations and nine (three polyvalent and six hyper-immune) intramuscular ig(i were investigated for specific content of anti-DNA. anti-F(ab')2 and antibodies reacting with several anti-DNA IgG Ids. Two samples (nos 6 and 11) showed high reactivity with allogeneic F(ah')b and with F(ab')b of myelornaprowins bearing the anti-DNA Id 31 and the 8.12%. Since both 31 and 8.12 Id markers are known to characterize pathogenic anti-DNA IgG in systemic lupus crythematosus (SLE). anti-Id antibodies to these markers were obtained by absorbing the IVIG samples nos 6 and 11 to Sepharose columns coupled with pooled F(ab')b fragments of 31+F4--8.12-myeloma proteins. inhibition experiments showed that anti-8.12%-eluted IgG induced a selective suppression of the DNA-reactive antibodies derived from patients with active lupus nephritis to their substrate. suggesting the involvement of KIT molecules in the SLE glornerular damage. Since 8.12% unti-DNA are nephritogenic antibodies, the occurrence of anti-8.12% in commercial IV1G may be of potential therapeutic relevance in modulating the pathogenic SLE Id network. Previous variable results of IV1G treatment in SLF. such as resolution of proteinum or worsening nephritis. could be related to variable enrichment of different lots of WIG in suppressive anti-pathogenic Id antibodies. [ABSTRACT FROM AUTHOR]

The IL-2/IL-2 receptor (IL-2R) system has been investigated in 64 patients with multiple myeloma (MM), 31 with monoclonal gammopathies of undetermined significance (MGUS) and 20 normal controls. The MM data were related to clinical status by comparing active disease, i.e. at diagnosis and at relapse, and stable disease, i.e. complete remission and off-treatment plateau phase. Serum and urinary values of the soluble IL-2R (sIL-2R) were significantly increased in MM patients compared with normal controls and this increase was related to activity. MM patients with active disease gave significantly higher values than those with stable disease. Compared with normal controls, enriched B cell (but not T cell) preparations from peripheral blood mononuclear cells (PBMC) showed significantly increased proportions of IL-2R+ cells in MM and MGUS. However, the highest proportions were detected in active MM compared with stable MM and MGUS, Also, 16% of all MM patients, as opposed to 9%, of MGUS, had well-defined bone marrow IL-2R+ plasma cell populations. The lowest serum IL-2 values were found in active MM. Serial follow up of serum sIL-2R suggested that this peptide can be used as an additional marker of active malignancy. The data indicate that a disturbance of IL-2/IL-2R system is most pronounced in active MM. These findings may provide clues as to the T cell abnormalities in MM. [ABSTRACT FROM AUTHOR]

Clinical, serological and cellular studies were carried out in five cases of Walden- ström's macroglobulinaemia with cryoglobulinaemia of the mixed IgM-IgG type and extremely high serum levels of rheumatoid factor activity. Clinically, no joint involvement or other distinctive features were found in these patients, as compared with other cases of primary macroglobulinaemia without ant-γ-globulin activity. The isolation of the monoclonal IgM immunoglobulins, as well as absorption studies with IgG and immuocytological investigations demonstrated that the whole of the rheumatoid activity was associated with the Waldenström-type paraproteins. Such cases seem to represent instances of a rheumatoid factor monoclonal gammapathy, in fact a subgroup of Waldenström's macroglobulinaemia. in view of the presence of an IgM paraprotein possessing anti-IgG activity, synthesized by the lymphocytoid cells infiltrating the bone marrow. [ABSTRACT FROM AUTHOR]

The article presents a scientific study, which reports the immunochemical quantitation of both serum and urine free light chains in a total number of seventy-five subjects with benign and malignant monoclonal gammopathies. In this study, the immunochemical quantitative determinations of both serum and urine free light chains were carried out in seventy-five subjects with a serum M-component. The results suggest that increased quantities of L-chain protein in serum and urine are a common feature of multiple myeloma and Waldenström's macroglobulinaemia. In benign monoclonal gammopathies such findings appear to be of less frequent occurrence.