OBJECTIVE: To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) . METHODS: Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression. RESULTS: Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range. CONCLUSION Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.
Humans ; Immunoglobulin Light Chains ; Immunoglobulin kappa-Chains ; Immunoglobulin lambda-Chains ; Latex ; Multiple Myeloma/diagnosis*

OBJECTIVE: To explore the clinical application value of serum light chain (sLC) in the diagnosis and therapeutic efficacy evaluation for multiple myeloma. METHODS: 46 patients with newly diagnosed multiple myeloma were selected as MM group and 50 healthy persons as control group. Rate scattering immunoturbidimetry was used to detect serum light chain and immunoglobulin (Ig) in two groups, serum protein electrophoresis was used to detect M protein by agarose gel. Then, the sensitivity and specificity of the two methods in MM diagnosis were analyzed and compared, and the significance of sLC detection in MM diagnosis were discussed. In addition, 15 MM patients after received conventional therapy were tracked, sLC levels in five different therapentic times were recorded, and the effect of sLC in efficacy evaluation of MM was analyzed. RESULTS: There were 11 cases of IgA type, 15 cases of IgG type, 8 cases of light chain κ type, 8 cases of light chain λ type, 2 cases of IgD type, and 2 cases of non-secretion type. The sLC-κ, sLC-λ and their ratio (including light chain type and double clone type), IgA and IgG (except IgD type), as well as albumin, beta-globulin and gamma-globulin levels showed statistically significant differences (P＜0.05) compared with the control group. The sensitivity of serum protein electrophoresis, Ig quantification, sLC and its ratio in the diagnosis of multiple myeloma were 57%, 76% and 65%, and their specificity were 83%, 61% and 90%, respectively. After the second or third chemotherapy, the sLC-κ/λ ratio gradually approached the normal range as the disease reliefes, and the sLC-κ/λ ratio continued to be on or off the line at outliers or further away from the reference value as the disease progresses in MM patients with κ type or λ type. CONCLUSION sLC detection shows positive significance in early diagnosis of multiple myeloma, SLC monitoring can be used for the efficacy evaluation for treatment of MM patients.
Humans ; Immunoglobulin kappa-Chains ; Immunoglobulin lambda-Chains ; Multiple Myeloma ; diagnosis

OBJECTIVE: To analyze the clinical significance of serum free light chain (sFLC) and sFLC-κ/λ ratio in patients with newly diagnosed multiple myeloma (MM), so as to provide the theoretical basis for the diagnosis, treatment and prognosis of MM patients. METHODS: A total of 43 patients newly diagnosed as MM in our hospital and 40 cases of other diseases that could cause sFLC increase were selcted. The clinical features of newly diagnosed MM patients were analyzed. On the basis of the type of sFLC, MM patients were divided into sFLC-κ and sFLC-λ group. The correlation of sFLC with clinical index in two groups was analyzed. The difference of sFLC-κ/λ ratio between MM and non-MM patients was analyzed. According to whether the involved/uninvolved sFLC ratio was greater than 100, the MM patients were divided into the low ratio and the high ratio group. The clinical index of these 2 groups were analyzed. RESULTS: Among MM patients, IgG type was the most. In sFLC-κ and -λ groups, the hemoglobin level negatively correlated with sFLC (r=-0.307, r=-0.494, P＜0.05), and the serum β2 microglobulin level positively correlated with sFLC (r=0.453, r=0.689, P＜0.05), and myeloma cells ratio also positively correlated with sFLC (r=0.307, r=0.309, P＜0.05). The concentration of albumin, lactate dehydrogenase and serum calcium did not correlate with sFLC (P＞0.05). The serum creatinine level also did not correlate with sFLC in the sFLC-κ group (P＞0.05), but in the sFLC-λ group they were obviously positive (r=0.697, P＜0.01). The ratio of sFLC-κ/λ ＜0.26 or ＞1.65 in MM patients was higher than that of non-MM patients, and the ratio of involved/uninvolved sFLC≥100 in MM patients was also higher than that of non-MM patients with statistically significant differences (P＜0.01). The levels of serum albumin, creatinine and β2 microglobulin, as well as myeloma cell ratio and ISS international staging of the patients between 2 groups were significantly different (P＜0.05), while the differences in sex, age and levels of hemoglobin, lactate dehydrogenase and blood calcium were not significant between the 2 groups (P＞0.05). CONCLUSION The light chain type λ in MM patients correlates with renal damage. The abnormalities of sFLC-κ/λ ratio occur mostly in MM patients. The MM patients with involved/uninvolosed sFLC ratio ≥100 show the severe symptoms and poor prognosis.
Humans ; Immunoglobulin Light Chains ; Immunoglobulin kappa-Chains ; Immunoglobulin lambda-Chains ; L-Lactate Dehydrogenase ; Multiple Myeloma ; Prognosis

A 53-year-old woman was admitted with epigastric discomfort and weakness. Laboratory examination at admission showed mild anemia and proteinuria. Esophagogastroduodenoscopy revealed marked mucosal atrophy, diffuse nodularity and granular appearance with mucosal friability. Biopsy was performed on the antrum and body of the stomach. On the next day, the patient began to complain of severe dyspnea, and hypoxia was present on pulse oximetry. Therefore, emergency echocardiography was conducted and it showed restrictive cardiomyopathy along with thrombus in the left atrium. With time, heart failure was aggravated despite intensive management. The result of gastric biopsy revealed amyloid deposits which stained positively with Congo red. On immunohistochemistry study, kappa and lambda chain were present. In addition, kappa chain was significantly elevated in urine and serum on electrophoresis. Although the patient was finally diagnosed as having primary gastric amyloidosis with restrictive cardiomyopathy, her general condition rapidly deteriorated and died at 12th hospital day. When obscure gastric lesion is encountered, performing gastric biopsy is strongly recommended since it be primary gastric amyloidosis. Herein, we present an unusual case of primary gastric amyloidosis.
Amyloidosis/complications/*diagnosis/pathology ; Endoscopy, Digestive System ; Female ; Heart Atria/diagnostic imaging ; Heart Failure/complications/*diagnosis ; Humans ; Immunoglobulin kappa-Chains/blood/urine ; Immunoglobulin lambda-Chains/blood/urine ; Immunohistochemistry ; Magnetic Resonance Imaging ; Middle Aged ; Stomach Diseases/complications/*diagnosis/pathology ; Thrombosis/diagnosis/diagnostic imaging ; Tomography, X-Ray Computed ; Ultrasonography

OBJECTIVETo investigate the clinical significance of serum free light chain (sFLC) detection in light chain multiple myeloma (LCMM).

METHODSA total of 37 newly diagnosed LCMM patients were enrolled in this study, including 17 patients with k light chain type and 20 patients with λ light chain type, the sFLC and 24 hours urine light chain (ULC) were measured before and after chemotherapy. The correlation of sFLC level with ULC and renal impairment was analyzed.

RESULTSAll the patients displayed an abnormally increased level of sFLC at diagnosis wtih median value of 105.44 mg/L and 146.39 mg/L for k and λ light chain types, respectively. The sFLC did not correlate with ULC before and after chemotherapy. Among the 12 patients with very good partial remission and normal ULC level, the sFLC still was abnormally increased in 8 patients. Renal impairment was associated with the urine λ-type light chain, and the area under the ROC curve of urine λ light chain at diagnosis is 0.792 (P = 0.031).

CONCLUSIONAll patients with LCMM show an abnormally increased level of sFLC at diagnosis. sFLC can be used to monitor the response to chemotherapy because it is more sensitive for analysis of therapeutic effect than urine λ light chain.

Humans ; Immunoglobulin Light Chains ; blood ; Immunoglobulin kappa-Chains ; blood ; Immunoglobulin lambda-Chains ; blood ; Multiple Myeloma ; blood ; drug therapy ; Renal Insufficiency

OBJECTIVETo study the clinicopathologic features, immunophenotype and gene rearrangement of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL).

METHODSSeven cases of PCLBCL were enrolled into the study. Clinicopathologic analysis, immunohistochemical staining and gene rearrangement for IgH and Igκ were undertaken in the study.

RESULTSAll the seven cases were male, and the median age was 72 years. Patients usually presented with multiple purple tumors, nodules, papules and infiltrative plaques. Two patients had a history of leg injury before onset, and one had mosquito bites. Histologically, the tumor involved the dermis and subcutis with dense and diffuse infiltrative pattern composing of centroblasts and/or immunoblasts. Immunohistochemical staining showed that seven cases (7/7) expressed CD20, six (6/6) expressed bcl-2, four (4/4) expressed MUM-1, four (4/5) expressed CD79a, four (4/5) expressed PAX-5 and four (4/6) expressed bcl-6, respectively. All cases did not express CD3ε, CD45RO, CD10 and CD30. IgH gene rearranged bands were detected in three (3/6) cases and Igκ was detected in one (1/5) case. Six of the seven cases died and the remaining patient, who was 44-year-old, was alive after 22 months of follow-up.

CONCLUSIONSPCLBCL is rare, predominantly affects elderly male patients. PCLBCL has poor prognosis and high mortality, but younger patients seem to have better prognosis. Some cases had a history of trauma or mosquito bites. The relationship between the history and the onset of PCLBCL needs further evaluation.

Aged ; Aged, 80 and over ; Animals ; Antigens, CD ; analysis ; Culicidae ; Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin kappa-Chains ; genetics ; Immunophenotyping ; Insect Bites and Stings ; complications ; Leg ; Leg Injuries ; complications ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Skin Neoplasms ; genetics ; pathology

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy.
Acid-Base Equilibrium ; Acidosis ; Beta-Globulins ; Biopsy ; Bone Marrow Examination ; Crystallins ; Drug Therapy ; Electrophoresis ; Epithelial Cells ; Fanconi Syndrome* ; Female ; Glycosuria ; Humans ; Hypophosphatemia ; Immunoglobulin kappa-Chains ; Kidney ; Middle Aged ; Multiple Myeloma* ; Plasma Cells ; Proteinuria ; Stem Cell Transplantation

A mediastinal mass was incidentally found on chest radiography in a 46-yr-old woman who had had myasthenia gravis (MG) for 2 months. Computed tomography revealed a 4-cm in size, well-defined, and lobulating mass with nodular calcification that was located in the thymus. Microscopically, the mass consisted of diffuse amorphous eosinophilic materials. These deposits exhibited apple-green birefringence under polarized light microscopy after Congo red staining. Immunohistochemical analysis revealed that they were positive for both kappa and lambda light chains and negative for amyloid A. A diagnosis of localized primary thymic amyloidosis was finally made. After thymectomy, the symptoms of MG were controlled with reduced corticosteroid requirements. Localized thymic amyloidosis associated with MG has not been reported to date.
Amyloidosis/complications/*radiography/*surgery ; Calcinosis/*radiography/*surgery ; Female ; Humans ; Immunoglobulin kappa-Chains/immunology ; Immunoglobulin lambda-Chains/immunology ; Mediastinum/radiography/surgery ; Middle Aged ; Myasthenia Gravis/*complications ; Radiography, Thoracic ; Thymectomy ; Thymus Gland/radiography/surgery ; Tomography, X-Ray Computed

Adult ; Aged ; Amyloidosis ; metabolism ; pathology ; Biopsy ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Immunoglobulin kappa-Chains ; metabolism ; Immunoglobulin lambda-Chains ; metabolism ; Intestinal Mucosa ; pathology ; ultrastructure ; Kidney ; metabolism ; pathology ; ultrastructure ; Kidney Diseases ; metabolism ; pathology ; Male ; Middle Aged ; Rectum ; pathology ; ultrastructure ; Retrospective Studies

OBJECTIVETo construct full-length human bladder cancer-specific antibody libraries for efficient display of full-length antibodies on the surface of mammalian cells.

METHODSThe total RNA was isolated from peripheral blood mononuclear cells from patients with bladder cancer. The repertoires of IgG1 heavy chain variable region (VH) and Kappa light chain were amplified by RT-PCR using specific primers. The antibody genes were inserted into the vector pDGB-HC-TM to construct the bladder-cancer-specific antibody libraries of heavy chains and light chains. Ten clones from each library were randomly picked for gene sequencing and transient transfection into FCHO cells to analyze antibody display on mammalian cell surface by flow cytometry after staining with corresponding fluorescent labeled antibodies.

RESULTSThe libraries of bladder-cancer-specific antibody heavy chain (IgG1) and light chain (LCk) were successfully constructed. Seven out of the 10 clones randomly selected from the heavy chain library and 9 out of the 10 clones from the light chain library showed correct open reading frame, coding for 7 unique VH and 9 unique LCk. The combinatory library size reached 3.32×10(11).

CONCLUSIONWe have successfully constructed a full-length human bladder-cancer-specific antibody library with a combinatory diversity of 3.32×10(11) based on mammalian display technology, which can be used for screening monoclonal antibodies against bladder-cancer-associated antigens.

Amino Acid Sequence ; Animals ; Antibodies ; genetics ; Cell Surface Display Techniques ; Gene Library ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin kappa-Chains ; genetics ; Peptide Library ; Urinary Bladder Neoplasms ; genetics ; immunology