增生性肾小球肾炎伴晶格状结构的单克隆IgG沉积

51岁男性,病程1月,以高血压起病,肾脏损害主要表现大量蛋白尿,低白蛋白血症,伴少量镜下血尿,肾功能异常。肾外表现有轻度正细胞正色素性贫血,血清免疫固定电泳提示κ型IgG单克隆免疫球蛋白条带,骨髓活检和骨髓细胞学检查均阴性。肾活检组织学改变为肾小球系膜细胞、内皮细胞增生,毛细血管袢内较多CD68+细胞浸润,肾小球基膜内皮下大量、少量系膜区、偶见上皮侧嗜复红物沉积,沉积物免疫荧光染色仅IgG1和κ轻链阳性,电镜观察沉积物具有晶格状结构,免疫电镜证实这些晶格状的物质IgG和κ轻链阳性。该患者最终诊断为增生性肾小球肾炎伴具有晶格状结构的单克隆IgG沉积。     

MALT B cell lymphoma with kidney damage and monoclonal gammopathy: a case study and literature review

We report a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) involving the left kidney and simultaneous onset of a monoclonal gammopathy IgM kappa. No predisposing local inflammatory condition was identified. Following left nephrectomy, the renal specimen showed the centrocyte like cells and lymphoid cells in the lymphoepithelial lesions were positive for CD20 and CD79α. The neoplastic cells expressed monotypic cytoplasmic IgM kappa. The demonstration of bone marrow cells of B-lineage expressing the same monoclonal protein as the tumor suggested bone marrow involvement, even in the absence of identical morphology. Despite chemotherapy and rituximab treatment, clinical follow-up showed right kidney extension with high-grade transformation, and finally systemic dissemination. This case illustrates that the kidney is among the sites that may be involved by MALT B-cell lymphomas in a primary or secondary fashion, and the need for expanded investigation of the possible dissemination. We review the literature on this unusual extranodal lymphoma.     

Characterization of a human plasmacytoma line

The TH line was established by bringing tumour cells from a multiple myeloma patient into suspension culture and subsequently cloning them by limiting dilution. The cultured cells show marked heterogeneity; there are ultrastructural differences between small and large TH cells, particularly with respect to the rough endoplasmatic reticulum (RER). Karyotyping revealed chromosome numbers in the triploid range, with many structural abnormalities, at the 14q32 region among others. A t(14;18) could not be demonstrated. TH was shown to have germline and a rearranged allele for kappa light chain, and only a single rearranged gene for heavy chain immunoglobulin. TH expressed PCA-1, CD9, CD28 and CD38 antigens, HLA class II, RER and kappa light chain, but few or no other antigens associated with the B-cell lineage. Light chain kappa and trace amounts of IgG3 were found intracellularly as well as in culture supernatant. The addition of IL-6 to cultures of TH increased proliferation, as well as the secretion of kappa light chain and the membrane expression of CD28 and CD38 antigens. Because TH has relatively few B cell markers on its membrane, it may be useful for the induction of monoclonal antibodies specific for human plasma cells. It also provides a model for the demonstration that IL-6 can act as a paracrine growth and differentiation factor for cells of myelomal origin.     

MALT lymphoma producing IgG-kappa type M-protein

A 72-year-old woman, who has been administered prednisolone and azathioprine with diagnoses of idiopathic thrombocytopenic purpura (ITP) and autoimmune hepatitis (AIH), underwent a complete medical examination because of monoclonal gammopathy (IgG-kappa). Tumors were found in the ileum and descending colon. Pathological examination of biopsy specimens suggested a diagnosis of marginal zone B-cell lymphoma of the MALT type with a high-grade component. Flow cytometric analysis by two-color staining revealed that the neoplastic B cells expressed CD38, CD19, IgG and kappa, but not CD5 or CD10. There were no abnormal plasma cells in bone marrow smears. The patient achieved complete remission after receiving three cycles of THP-COP chemotherapy, which resulted in a decrease of the IgG level to within the normal range. These findings indicated that monoclonal IgG-kappa might be produced by lymphoma cells. However, the relationship of the immunosuppressive agents to the pathogenesis of the MALT lymphoma remains to be clarified.     

Human monoclonal anti-cytomegalovirus antibodies

Specific human monoclonal anti-CMV antibodies have been isolated and characterized. The first patient had a chronic T cell lymphocytic leukaemia and a subclinical CMV infection developed at the same time as a monoclonal peak of kappa IgG3. The purified F (ab')2 fragment of the IgG3 had an intense anti-CMV activity. A second monoclonal antibody, also a kappa IgG3, was isolated in a non-immunodepressed patient with a primary CMV infection (chronic pyrexia and hepatitis). The immunotransfer showed that the anti-CMV IgM and IgG of the patient's serum reacted particularly with the p51 protein of virus capsid. The monoclonal IgG3 was specific for the same p51. The third monoclonal anti-CMV Ig studied was synthesized in vitro by the B lymphocytes of a renal transplant patient immortalized by the Epstein-Barr virus. This kappa IgM produced continuously reacted strongly with the nucleus of the cells infected by the CMV. Human monoclonal anti-CMV antibodies could be used for the early detection of viral antigens by immunofluorescence and might also be used to treat severe cases of CMV infection.     

IgG-secreting lymphoplasmacytoid leukaemia: a B-cell disorder with extensively mutated VH genes undergoing Ig isotype-switching frequently associated with trisomy 12

We investigated 16 patients with elevated serum monoclonal IgG and a leukaemic B-cell lymphocytic disorder different from multiple myeloma. Their clinical history was that of a non-aggressive disease with dominant splenomegaly and long survival. Whereas abnormal blood and bone marrow cells were predominantly small lymphocytes with a few lymphoplasmacytoid cells, histopathological features included a lymphoplasmacytic infiltrate in eight cases. Most frequently, abnormal blood cells displayed a CD19+CD5-CD23+/- immunophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19+CD5+CD23+ phenotype. Interestingly, a coexistent serum monoclonal IgM and/or surface IgMG+ with identical light chain was identified in 10 patients, whereas in the remaining six patients only IgG expression was determined. VH gene analysis was performed in eight patients to investigate the clonal origins of tumour cells. All cases utilized the VH3 family, with evidence of extensive somatic mutations and intraclonal homogeneity in all cases. VH gene analysis indicated a clonal relationship between cells expressing IgM and IgG, with one case being biclonal. Cytogenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-grade lymphoma with high-serum IgG and frequent lymphoplasmacytoid features in which tumour cells derive from post-follicular memory B cells undergoing isotype switching with some cases arrested at both the IgM and IgG stage and others as IgG-positive cells only.     

Index of light kappa/lambda and lambda/kappa chains in monoclonal gammopathies

Concentrations of the light chains kappa and lambda were determined by simple radial immunodiffusion in the blood sera of 437 patients with monoclonal gammopathies. The kappa/lambda index was calculated in monoclonal gammopathies with the antigenic type of kappa light chains, while in monoclonal gammopathies with the antigenic type of lambda light chains the lambda/kappa index was calculated. The results obtained in malignant monoclonal gammopathies were compared with the results obtained in monoclonal gammopathies of undetermined significance for IgG and IgM paraproteinemias. Differences of high statistical significance were established (for IgG and IgA p less than 0.001, for IgM p less than 0.005) and thus the light-chain index can be used as another marker in differential diagnosis of monoclonal gammopathies.     

Treatment of severe Epstein-Barr virus-induced polyclonal B-lymphocyte proliferation by anti-B-cell monoclonal antibodies. Two cases after HLA-mismatched bone marrow transplantation

We treated two children who developed Epstein-Barr virus-induced polyclonal B-cell proliferation after HLA-mismatched bone marrow transplantation for congenital immunodeficiency with two monoclonal anti-B-cell antibodies. Lymphoproliferative syndrome occurred between 50 and 60 days after bone marrow infusion, and was diagnosed by the presence of spontaneously growing B cells containing Epstein-Barr-nuclear antigen in the blood and bone marrow. The mouse monoclonal anti-B-cell antibodies used were a CD21-specific antibody recognizing the CR2 receptor on B cells (BL13, IgG1) and a CD24-specific antibody binding B cells at all steps of differentiation (ALB9 IgG1). Both antibodies were given intravenously (0.2 mg/kg/body weight.d for 10 days). All clinical and biological manifestations resolved within 3 weeks of treatment. Recurrence was not seen at 18- and 15-month follow-ups. T-cell function developed normally; B-cell function remained partially deficient in one patient 21 months after bone marrow transplantation. These results suggest that monoclonal anti-B-cell antibodies could be useful in controlling severe polyclonal lymphoproliferative syndrome in profoundly immunodeficient patients after bone marrow transplantation.     

Primary MALT lymphoma of the kidney

A primary mucosa associated lymphoid tissue tumor (MALT) of the kidney in a 50-year-old man who suffered from on therapy resistant high blood pressure over 15 years period is presented. A mass in the right kidney (6x5x3 cm) during routine check up was discovered on ultrasonography and confirmed on CT scan and NMR. The patient was submitted to nephrectomy. A mass involving kidney, pyelon and upper part of the ureter was found. Histology showed low grade non-Hodgkin B-cell lymphoma of MALT type. The neoplastic cells were positive for monoclonal antibodies CD20, CD79alpha, surface and cytoplasmic and IgM immunoglobulins and showed light chain restriction (kappa+). After histology was available, a careful staging was performed. The disease was not found anywhere else. It was concluded that the patient belonged to the stage IE of primary kidney MALT lymphoma. Gastroscopy showed signs of chronic superficial gastritis. Urease test was positive and IgG antibodies against Helicobacter pylori in titer 421 were found as well. Except for Helicobacter pylori no additional therapy was given.     

Amyloid-Associated Muscle Pseudohypertrophy and Multiple Myeloma in a Man with Hypernephroma

ABSTRACT. Amyloidosis is known to occur both in renal adenocarcinoma and multiple myeloma. This paper describes a 52-year-old man who developed multiple myeloma and widespread amyloidosis after surgical removal of a hypernephroma. Multiple myeloma presented with osteolytic bone lesions and slight bone marrow plasmocytosis. Both kappa light chains and monoclonal IgG were secreted. Amyloidosis was seen as muscle pseudohypertrophy with wood-hard masses of amyloid in shoulders, girdle, buttocks and proximal limbs. Macroglossia was impressive and swelling of submandibular structures and the floor of the mouth was marked. Knowing the peculiar immunological potency of hypernephroma, attention is called to associations between renal carcinoma and monoclonal gammopathies, including amyloidosis.     

Heavy and light chain primary structures control IgG3 nephritogenicity in an experimental model for cryocrystalglobulinemia

Crystal formation by monoclonal immunoglobulins is a well-known but rare complication of B-cell neoplasia. We have designed an in vivo model of cryocrystalglobulinemia by grafting to mice hybridoma clones producing a pathogenic monoclonal immunogloblulin (Ig) G3kappa. One clone, 8A4, secreted a singular IgG3 that formed crystals both in the proliferating plasma cells and as mesangial and subendothelial deposits in the kidney glomeruli. Morphologic analysis of kidneys revealed neutrophil infiltration and endocapillary hyperplasia, while the morphology of deposits was reminiscent of those in cryocrystalglobulinemia patients. A variant clone that only differed from 8A4 by a 3-amino acid deletion in the V(kappa) CDR1 increased its secretion level by 7-fold and produced an abundant bona fide serum monoclonal cryoglobulin in mice, without crystal formation within tumoral cells; it yielded no subendothelial deposits but only amorphous precipitates in capillary lumens of kidney glomeruli, reminiscent of those seen in the human hyperviscosity syndrome, without other glomerular lesions. A limited variation in the V(kappa) domain thus proved able to increase secretion, to abrogate crystallization, and to modify patterns of glomerular lesions and deposits. Both the crystallizing and noncrystallizing IgG3kappa sequences were related to previously reported murine cryoglobulins, all including a gamma3 chain and canonical VH sequences. Two additional variants of 8A4 with identical VH and VL domains but having switched to IgG1 also lost crystal formation, further showing this feature of 8A4 to result from a unique 3-dimensional conformation of the complete immunoglobulin, relying on V and C domain primary structures of both chains.     

Transient expression of a second monoclonal component in two forms of biclonal gammopathy

Two cases of transient biclonal gammopathy are described, one having an IgG kappa and an IgA kappa monoclonal component and another with IgG1 kappa and IgG4 kappa monoclonal components. In both of these cases the second monoclonal component gradually disappeared. Anti-idiotypic antibodies were made against the major monoclonal serum component; in the first case the idiotype of the IgG kappa clone was not found in the IgA kappa plasma cells (real biclonal gammopathy) whereas in the second case the idiotypes of the two clones were identical (apparent biclonal gammopathy). The evolution to monoclonal gammopathy is discussed with regard to the existence of common malignant precursor cells in biclonal gammopathy.     

Detection of Rh D-associated epitopes in human and animal tissues using human monoclonal anti-D antibodies

The distribution of Rh D-associated epitopes in human and animal tissues has been assessed by immunochemical techniques using six human monoclonal anti-D antibodies. The IgM antibody MAD-2 reacted predominantly with endothelial cells lining blood vessels and with animal leucocytes and human leucocytes from both Rh D-positive and Rh D-negative donors. Immunoblotting revealed reactivity with a 55 kDa tissue component which was most prominent in homogenates of heart, lung and spleen. In contrast, the IgG antibodies UCHD4 and FOG-1 stained smooth muscle, and UCHD4 in addition weakly stained cardiac and skeletal muscle and the glomeruli of kidney. Immunoblotting with UCHD4 revealed reactivity with a 27 kDa tissue component which was most prominent in heart homogenates. The results show that the six monoclonal anti-D antibodies recognize at least four different epitopes and that Rh D-associated epitopes may occur in non-erythroid cell types.     

晚期血吸虫病患者脾切除对免疫功能的远期影响

目的探讨脾切除对晚期血吸虫病（晚血）患者体液免疫和细胞免疫的远期影响。方法选择晚血肝纤维化Ⅲ级合并腹水病人55例,分为脾切除组与非脾切除组,抽取周围静脉血检测白细胞（WBC）、红细胞（RBC）、血小板（PLT）、嗜酸性粒细胞（EOS）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）、谷氨酰转肽酶（GGT）、白蛋白（A）、总胆红素（TB）、Ⅲ型前胶原（PC-Ⅲ）、Ⅳ型胶原（Ⅳ-C）、透明质酸（HA）、IgG、IgA、C3、C4、CD3、CD4、CD8、CD56＋16。结果非脾切除组TB（27.75±13.11）μmol/L,ALT（27.66±12.82）U/L,ALP（157.16±72.29）U/L,GGT（86.34±92.40）U/L,A（37.76±6.21）g/L,HA（156.32±86.89）mg/L,Ⅳ-C（74.49±23.92）μg/L,PC-Ⅲ（146.53±69.60）mg/L,IgG（20.60±6.12）g/L、IgA（4.45±2.23）g/L、C3（0.66±0.23）g/L、C4（0.14±0.04）g/L,CD3（63.64±11.08）%、CD4（37.59±8.33）%、CD8（21.46±8.74）%、CD56＋16（15.58±8.52）%,WBC（2.59±1.08）×109/L,PLT（39.00±16.96）×109/L。脾切除组TB（23.83±14.37）μmol/L,ALT（25.74±11.81）U/L,ALP（179.00±89.06）U/L,GGT（100.59±69.96）U/L,A（3.16±6.01）g/L,HA（25.66±130.72）mg/L,Ⅳ-C（6.86±42.77）μg/L,PC-Ⅲ（53.69±72.35）mg/L,IgG（7.24±11.66）g/L、IgA（6.11±2.14）g/L、C3（0.69±0.18）g/L、C4（0.13±0.05）g/L,CD3（8.07±11.67）%、CD4（6.76±7.56）%、CD8（9.98±11.25）%、CD56＋16（8.18±12.24）%,WBC（5.23±1.54）×10^9/L,PLT（146.41±57.94）×10^9/L,两组肝功能与肝纤维化水平无明显差异,脾切除组WBC、PLT、IgG、IgA、CD56＋16升高,CD3、CD4和A下降。结论晚血患者脾切除后,WBC与PLT升高,细胞免疫下降,体液免疫增强。     

Spontaneous Epstein-Barr virus transformed B-cell line sharing the identical immunoglobulin gene rearrangement with acute myeloid leukemia

Mononuclear cells from a 44-year-old patient with acute myeloid leukemia (AML) gave rise to a spontaneous permanent cell line cultured in suspension. The cell line was shown to be positive for Epstein-Barr virus nuclear antigen (EBNA). As expected, its composite phenotype was of B-cell type with B-cell antigens (CD 20, CD 21) and with monoclonal surface IgM of kappa type, but without detectable IgM secretion. Surprisingly, identical monoclonal rearrangements of the immunoglobulin heavy chain (JH) sequences could be demonstrated in the uncultured bone marrow AML cells and in the cell line that also had kappa light chain gene rearrangement. This is the first case to our knowledge of an EBNA positive B-cell line with identical monoclonal Ig heavy chain rearrangement as detected in myeloblastic leukemia cells.     

Solitary plasmocytoma of the vagina

A 78-year-old woman with a plasmocytoma of the vagina is described. The diagnosis monoclonal IgG kappa-producing plasma cell tumour was based on immunohistochemical studies. Careful screening for other localizations including immunofluorescence of the bone marrow aspirate and in methyl-methacrylate embedded bone marrow biopsy specimen, yielded no evidence in favour of a multiple myeloma. To our knowledge only 5 patients with plasmocytoma of the vagina were previously reported, but only in the present case extensive immunohistochemical studies of tumour, bone marrow and blood were performed.     

Multiple organ relapse in primary de novo CD5+ diffuse large B cell lymphoma of the bone after a complete response

A 57-year-old woman was admitted with swelling of the femur. MRI showed that an intramedullary lesion had expanded from the trunk to the distal portion where it had formed an extramedullary tumor mass. An open biopsy showed diffuse proliferation of abnormal lymphoid cells. Immunohistochemical staining and flow cytometry demonstrated LCA+, CD3-, CD23-, CD79a+, CD5+, IgM+, IgD- and kappa + and cyclin D1-. FISH analysis did not detect t(11;14)(q13;q32). The final diagnosis was de novo CD5+ diffuse large B-cell lymphoma (DLBL) of the bone at clinical stage IEA. The patient suffered a pathological fracture in the femur after two courses of CHOP. The therapy was changed to ESHAP and irradiation. The result was assessed as a complete remission (CR). One month later, the patient presented with epigastric pain. MRI showed the tumor at the spleen and kidney and hydronephrosis due to pelvic lymphadenopathy, but did not show a tumor in the femur. An open biopsy of the pelvic lymph node showed relapse. The tumor and hydronephrosis disappeared and necrosis in the kidney was observed on MRI after ESHAP. De novo CD5+ DLBL appears to constitute a unique subset of DLBL with an aggressive clinical course and requires established therapeutic strategies.     

A rare case of extramedullary plasmacytoma in the mediastinum.

A rare case of extramedullary plasmacytoma in the mediastinum is reported. An 80-year-old man was admitted for further examination of a mediastinal tumor. Chest computed tomography (CT) revealed a large mediastinal mass and right interlobar pleural effusion. Needle biopsy under CT guidance established a diagnosis of plasmacytoma. Immunohistochemical staining revealed that the tumor cells were producing monoclonal IgA kappa. Serum immunoelectrophoresis revealed an IgA kappa monoclonal component with a serum concentration of 5,040 mg/ml. The bone marrow aspiration was normal. Bone roentgenogram and bone scintigram showed osteoporosis but no neoplastic lesion.     

Splenic marginal zone B-cell lymphoma with bilateral renal invasion after splenectomy

A 61-year-old woman presented with hepatosplenomegaly, systemic lymphadenopathy, anemia, and thrombocytopenia. Peripheral blood and bone marrow examination showed atypical lymphoid cells with villi. Immunophenotyping of these cells was CD19+CD20+CD5-CD10-CD23-, and light chain restriction (kappa) was positive. To confirm the diagnosis histologically, we performed a splenectomy and diagnosed the patient's disease as splenic marginal zone lymphoma (SMZL). She rapidly recovered normal hematological parameters and gallium-67 citrate scan showed no increased uptake. Two months after the splenectomy, however, she was readmitted with findings of 15% blasts in the peripheral blood and massive infiltration of the bone marrow by large blastoid cells. Laboratory evaluations were positive for monoclonal IgM-kappa protein. Under acute renal dysfunction, we performed a CT scan that showed bilateral enlargement of the kidneys with features suggestive of an infiltrative process besides systemic lymph node enlargement. A kidney biopsy established the diagnosis of lymphoma with renal infiltration. SMZL is characterized by an indolent clinical course, and no previous report has described SMZL with bilateral renal invasion. Complete remission was obtained after 3 cycles of chemothreapy (R-CHOP). She is undergoing 3 more courses and remains in remission 6 months after the rapid progress of her illness.     

Immunohistological analysis in diagnosis of plasma cell myeloma based on cytoplasmic kappa/lambda ratio of CD38-positive plasma cells

Abstract

The accurate determination of cytoplasmic immunoglobulin (cIg) light chain (LC) expression is important to differentiate reactive plasmacytosis from a clonal plasma cell neoplasm such as plasma cell myeloma (PCM). Through retrospective analysis, we studied the cytoplasmic kappa/lambda ratio of CD38-positive plasma cells in the bone marrow from 19 PCM patients and 19 controls. To demonstrate cIg LC expression, the bone marrow was immunostained for IgA, IgG, IgM, kappa, and lambda. The kappa/lambda ratio was defined as the ratio of the kappa-positive cell to the lambda-positive cell in plasma cells. PCM cells were distinguished from normal plasma cells by cut-off levels between 0.59 and 4.0, a sensitivity of 94.7%, and a specificity of 94.7%. The detection of the cytoplasmic kappa/lambda ratio of CD38-positive plasma cells may be a useful tool in the diagnosis of PCM and the correct diagnosis of PCM may be achieved more simply.