M蛋白阳性患者314例体液免疫特征分析

[目的]分析314例血清蛋白电泳M蛋白阳性患者血尿免疫学特征及其相关性。[方法]对华西医院门诊及住院患者采用琼脂糖凝胶电泳法作血清蛋白电泳检测,检出M蛋白带的患者,再作免疫球蛋白G、A、M、血轻链Kappa(κ)、Lambda(λ)和Kappa/Lambda(κ/λ)比值、尿游离轻链Kappa(κ)、Lambda(λ)检测,用免疫固定电泳鉴定M蛋白类型,采用t检验、配对秩和检验和相关分析比较其血尿蛋白免疫学特征及其相关性。[结果]3156例血清蛋白电泳筛检出M蛋白阳性314例,其中IgG型所占比例最大(66.6%)。血清蛋白电泳后,IgG和IgM型M带主要分布于γ区,较少分布在α2和β区;IgA型M带主要分布在γ区,其次分布在β区,较少分布在α2区。IgG、IgA、IgM型患者对应Ig的血清浓度均显著升高(P﹤0.01),IgG和IgA型患者的非对应Ig血清浓度明显低于正常(P﹤0.01),IgM型患者的IgG浓度明显低于正常(P﹤0.01),而IgA浓度略有降低但并不显著。M蛋白类型对应轻链的血清浓度均显著增高(P﹤0.01),非对应轻链均在正常范围内;各类型患者血清κ/λ值均明显异常。以免疫固定电泳的结果作为参考,观察各指标检测M蛋白的能力,其敏感性依次为血清κ/λ98.1%,血清Ig97.1%,血清轻链96.2%,尿轻链78.1%。[结论]应用免疫固定电泳结合血清蛋白电泳及免疫球蛋白定量等方法可以比较敏感地检测出M蛋白,并对其进行分类、分型,为临床诊断和治疗提供重要依据。     

51例多发性骨髓瘤的临床特点分析及实验室指标的诊断意义

目的：了解多发性骨髓瘤（MM）的临床特点,减少误诊、漏诊,并探讨实验室检查对MM的诊断意义。方法回顾性分析51例MM患者临床资料。结果：①40例MM被误诊,占78.4%。②骨痛和乏力是最常见首发症状,分别为21例（41.2%）,18例（35.3%）。③51例MM分型以IgG型最多（26例,51.0%）,其次为IgA型11例,轻链型10例。④49例MM免疫固定电泳检出M蛋白,其对应的免疫球蛋白（Ig）均有不同程度升高,而其他正常的Ig降低。⑤49例MM血清游离轻链κ/λ异常,并且存在比值失衡现象（即一种轻链升高,另一种轻链降低）。⑥51例MM骨髓检查均检出浆细胞。结论：MM的临床表现复杂,容易误诊;免疫固定电泳和骨髓穿刺检查是诊断MM的重要指标;Ig及游离轻链检测对诊断MM有筛查作用。     

血清蛋白电泳对多发性骨髓瘤诊断的临床应用

目的：探讨血清蛋白电泳检测对多发性骨髓瘤（MM）的诊断价值。方法：对本院门诊及住院患者采用琼脂糖凝胶电泳法作血清蛋白电泳检测,检出M带的患者,再作免疫球蛋白G、A、M、轻链Kappa、Lambda、及Kappa/Lambda比值、总蛋白、球蛋白检测,并作回顾性分析。结果：12049例蛋白电泳检出M蛋白条带210例,占1.74%,其中确诊为MM的15例,占M蛋白血症的7.1%。血清Kappa测定结果：κ型多发性骨髓瘤显著高于健康组（P〈0.001）,λ型多发性骨髓瘤显著低于健康组（P〈0.001）,良性M蛋白病稍高于健康组（P〈0.05）。血清Lambda测定结果：κ型多发性骨髓瘤显著低于健康组（P〈0.001）,λ型多发性骨髓瘤显著高于健康组（P〈0.001）,良性M蛋白病稍低于健康组（P〈0.05）。血清κ/λ比值测定结果：κ型多发性骨髓瘤显著高于健康组（P〈0.001）,λ型多发性骨髓瘤显著低于健康组（P〈0.001）,良性M蛋白病与健康组相比（P〉0.05）,IgG、TP、GLB多发性骨髓瘤显著高于良性M蛋白病组（P〈0.001）。结论：血清蛋白电泳中M蛋白的检查是早期发现多发性骨髓瘤的敏感方法。     

慢性肾功能不全患者免疫球蛋白及补体测定的临床意义

[目的]探讨血清中免疫球蛋白IgG、IgA、IgM及其轻链κ和λ含量、κ/λ比值以及补体C3、C4、B因子(PFB)含量在慢性肾功能不全(CRT)诊疗中的应用价值.[方法]在特定蛋白仪上,采用免疫速率散射比浊法测定IgG、IgA、IgM及其κ和λ含量以及C3、C4、PFB含量,并且计算κ/λ比值.[结果]与36例正常对照组比较,49例CRF患者血清中免疫球蛋白IgG、IgM,C3含量及κ/λ比值均降低,而免疫球蛋白IgA、轻链λ和C4含量则均升高.[结论]血清中免疫球蛋白IgG、IgA、IgM及其轻链κ和λ含量、K/k比值以及补体C3、C4、PFB含量检测对CRF的临床诊疗有重要的意义.     

免疫固定电泳检测在多发性骨髓瘤分型诊断中的应用价值

目的：探讨与评价免疫固定电泳在多发性骨髓瘤（MM）分型诊断中的应用价值.方法：采用全自动Spife 3000电泳仪,对84例经临床确诊的MM患者进行免疫固定电泳分析.结果：在84例MM患者中均呈现M蛋白,阳性率100％,其中以IgG型为主（66.7％）,其次为IgA型（29.8％）,而IgM型仅1例（1.2％）,轻链型2例（2.4％）.结论：免疫固定电泳对M蛋白的检测具有敏感性好、特异性强和分辨率高的特点,可作为MM分型诊断的重要依据,并在病情监测、疗效评估和指导治疗等方面具有重要作用.     

4种电泳及轻链定量在多发性骨髓瘤诊断中的应用

目的探讨4种电泳筛查多发性骨髓瘤(multiple myeloma, MM)及其分型的价值。 方法收集我中心164例MM患者作为病例组(MM患者组),同时收集45例健康体检者作为对照组(非MM组),所有研究对象均采集血液和尿液。用血清蛋白电泳(serum protein electrophoresis,SPE)和高分辨尿蛋白电泳(high resolution urinary protein electrophoresis,HR)分别对所有研究对象的血液和尿液样本进行M蛋白筛查,然后用血清免疫固定电泳(immunofixation electrophoresis,IFE)和尿本周氏蛋白电泳(Bence-Jones protein electrophoresis,B-J)对所有研究对象进行分型;并用罗氏生化仪检测所有研究对象的血清总蛋白(total protein,TP)、白蛋白(albumin,ALB)、球蛋白(globulin,GLOB)、免疫球蛋白(immunoglobulin,Ig)及轻链定量,并计算轻链比值。 结果SPE和HR对164例MM患者M蛋白的检出率分别为92.68%和59.76%,IFE和B-J的检出率分别为98.17%和59.76%。45例非MM组经4种电泳均未检出M蛋白。与非MM组相比较,MM患者组的TP、GLOB、轻链κ、λ含量显著升高,差异有统计学意义(t=34.968,38.231;F=72.811,58.611;P<0.05)。轻链型患者HR、B-J的阳性率明显高于IgA型患者、IgG和IgM型患者,差异具有统计学差异(χ²=6.870,13.236,19.725;P<0.05)。 结论IFE是MM诊断最敏感的检测方法,使用多种电泳方法结合免疫球蛋白及轻链定量同时检测,可以明确分型,有效避免漏诊、误诊,为临床全面评估病情提供依据。     

尿液轻链κ,λ在多发性骨髓瘤诊断中的临床价值

目的探讨多发性骨髓瘤(MM)患者尿液轻链κ,λ在MM诊断中的临床价值。方法采用速率散射免疫比浊法同时检测106例MM患者及30例健康对照者的尿液轻链κ,λ,评价其对MM的临床诊断价值。结果发现106例MM患者与正常对照组比较,γ-球蛋白均显著增高(P0.01),而其他蛋白与对照组相比较无明显改变(P0.05)。同时,106例MM患者与正常对照组尿液轻链κ,λ比较,κ,λ均显著增高(P0.01)。多发性骨髓瘤起病徐缓,可有数月至十多年无症状期,早期易被误诊。尿液游离轻链检测不存在上述做免疫固定电泳所需按重浓度稀释问题,并且为定量检测,且游离κ和λ不受肾脏功能及尿量影响,有较好的特异性和灵敏性。结论检测尿液轻链κ,λ,可及早预防多发性骨髓瘤,且检测方法简便、快速、无创伤,不会对患者造成痛苦,对MM具有较高的临床诊断价值。     

134例维吾尔族多发性骨髓瘤患者血清免疫球蛋白及轻链检测分析

目的对新疆维吾尔族患者在多发性骨髓瘤诊断中免疫球蛋白及轻链检测的临床应用进行分析和探讨。方法针对134例多发性骨髓瘤患者利用免疫散射比浊法检测血清免疫球蛋白及轻链,60例健康体检者作为对照组。结果研究组中Ig G型最多,其次为Ig A型、Ig M型,且Ig G型的Ig G含量、Ig A型的Ig A含量和Ig M型的Ig M含量均明显高于对照组,差异有统计学意义(P0.05)。研究组中不同类型的轻链κ、轻链λ间差异有统计学意义,且与对照组比较差异也有统计学意义(P0.05)。κ型MM患者血清κ浓度升高,λ浓度普遍降低,κ/λ比值明显高于对照组。λ型MM患者血清λ浓度升高,κ浓度普遍性降低,κ/λ比值明显低于对照组。κ/λ比值在不同类型MM患者中表现不同,λ型1,而κ型2。结论血清中免疫球蛋白及轻链可以较好的作为多发性骨髓瘤的临床诊断标记物,对各种分型具有较好的参考价值,对临床诊断及治疗有重要意义。     

M蛋白对多发性骨髓瘤的诊断价值

目的分析M蛋白对诊断多发性骨髓瘤的临床应用价值。方法择取2014年1月至2017年1月本院收治的98例多发性骨髓瘤(MM)患者为研究对象,对其进行常规化M蛋白、细胞形态学、尿轻链以及血清免疫球蛋白检测,分析结果。结果 98例病患中IgA者20例,IgG者32例,轻链型38例,不分泌型8例。初诊时,M蛋白未达到国内IgG标准(35 g/L)者4例,未达到IgA标准(20 g/L)者2例。初诊时,M蛋白定量者60例,M蛋白分析值为0.85~116 g/L,白细胞计数为(1.9~9.7)×10~9/L,血红蛋白(Hb)为31~129 g/L,骨髓瘤细胞为5%~90%,血小板计数(PTL)为(36~369)×10~(12)/L;发现骨质破坏/骨折者44例。经相关性分析可见,初诊IgG以及IgA者与M蛋白和M细胞负荷为正相关(r=0.551、0.766,P0.05),初诊IgG以及IgA者与Hb呈现负相关(r=-0.463、-0.745,均P0.05),初诊IgG以及IgA者与轻链型呈现负相关(r=-0.639,P0.05)。肾功能不全IgG者4例,IgA者14例,轻链型12例。IgG者肾功能受损发生率较IgA型/轻链型更低,组间比较差异均具有统计学意义(P0.05)。结论M蛋白为诊断MM以及判断临床分期的重要性指标之一,值得进一步深入研究。     

31例多发性骨髓瘤细胞形态学与其它实验室常用指标的综合分析

目的:探讨多发性骨髓瘤(MM)的细胞形态学、白球蛋白比例(A/G),血清蛋白电泳、血清免疫固定电泳,在疾病诊断中的作用。方法:回顾性分析31例多发性骨髓瘤细胞形态学特点,实验室常用指标和临床特点。结果:31例MM病例中:骨髓涂片中骨髓瘤细胞比例在(10%~20%)的6例(19.4%),骨髓瘤细胞比例在(21%~30%)的2例(6.4%),骨髓瘤细胞比例在(31%~85.5%)的20例(64.5%),骨髓瘤细胞比例〈10%的3例(9.7%);血清蛋白电泳有M蛋白的26例(83.3%);血清免疫固定电泳:IgG型18例(58.1%),IgA型8例(25.8%),轻链型5例(16.1%);白球蛋白比例(A/G)倒置的24例(77.4%)。结论:骨髓细胞形态学检查是诊断MM的主要方法。血清学特点和临床表现对MM的诊断有提示作用,三者需紧密结合。     

Prognostic significance of the immunological variant in patients with multiple myeloma.

INTRODUCTION: The prognostic significance of the immunological variant and especially of the type of light chain secretion in multiple myeloma is controversially assessed in the literature. OBJECTIVE: To study the prognostic significance of the class and type of the monoclonal production in patients with multiple myeloma. PATIENTS AND METHODS: 109 patients with multiple myeloma were enrolled, in the study, diagnosed and treated at the University Clinic. The class and type of the paraprotein secretion was determined using immune electrophoresis of serum and/or urine by Grabar and Williams, Mancini radial immunodiffusion and Ouchterlony immunodiffusion for light chain typing. The median survival (MS) was calculated using the method of maximal logarithmic authenticity, where the survival in months = log t. RESULTS: The MS of all patients was 29 months. Patients with Bence Jones myelomas showed the lowest survival--12 months; followed by those with IgD myelomas--20 months. The patients with combined and non-combined light chain production (BJ+) lived 26 months, with BJ(-)--35 months (inauthentic difference). No difference was found between the survival of BJ(kappa)--30 months and BJ(lambda)--21 months. BJ(+) patients with myeloma nephropathy and nitrogen retention had a MS of 23 and 20 months, respectively, as compared with the BJ(+) patients without myeloma nephropathy and nitrogen retention: 47 and 40 months (p < 0.05). DISCUSSION AND CONCLUSION: The class of the paraprotein secretion only and the two types of light chain separately do not possess any prognostic significance. From a quantitative point of view the class and type of paraprotein production are independent staging criteria with certain predictive value. The prognostic significance of BJ-proteinuria is found making comparison between the groups in which its pathogenic effect is expressed.     

Antigen nature and complexity influence human antibody light chain usage and specificity

Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145 μg/mL kappa, 2.82 μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies.     

Plasma electrolytes in multiple myeloma

The plasma cell myeloma (multiple myeloma, myelomatosis) is a progressive disease, characterized by bone marrow plasmacytomas and the presence of monoclonal antibodies (IgG, IgA, IgD, IgE), or free kappa or lambda immunoglobulin side chains. The monoclonal antibodies or Bence-Jones protein may precipitate in the tubuli and impair kidney function. In addition, the plasma protein concentration may increase at the expense of plasma water level causing unrealistically low electrolyte levels. Since the isoelectric points of immunoglobulins are higher than those of most other plasma proteins, the net charge of plasma proteins may change causing new electrolyte balance. In addition, some monoclonal antibodies are more hydrated than others, and their high concentration may cause not only increased plasma viscosity but further electrolyte imbalance. In the present work the relationship between plasma protein and electrolyte levels is studied in samples of 100 multiple myeloma patients.     

Amyloidosis induced colonic stricture. The first symptom of myeloma multiplex. A case report

Systemic amyloidosis often involves the gastrointestinal tract and usually presents as ulceration or polypoid lesions. However, annular stricture of the colon due to amyloidosis is very rare. Amyloidosis develops in appr. 10% of multiple myeloma patients with lambda light chain production, it is usually type AL and not a presenting symptom. CASE REPORT: A 73-year-old female patient appeared at our hospital with anaemia, abdominal pain and haematochesia. Colonoscopy revealed a circular narrowing of the sigmoid colon suggesting malignancy. The patient underwent sigmoid resection and rectosigmoideal anastomosis was prepared to relieve mechanical obstruction. Surprisingly the histological finding from the resected specimen was amyloidosis. Subcutaneous fat tissue biopsy established the diagnosis of systemic AA amyloidosis. Immunoelectrophoresis revealed an elevated gamma-globulin fraction with IgG lambda monoclonal component, as well as a different lambda light chain. Therefore bone marrow biopsy was carried out which confirmed the diagnosis of multiple myeloma. DISCUSSION: Our case is a rare example of the extraordinary tumor-mimicking colon amyloidosis that led to the diagnosis of multiple myeloma. Beside haematological treatment, strict follow-up of the colon process and reconsideration of surgical therapy or endoscopic stenting is of great importance.     

多发性骨髓瘤肾脏损害的临床分析

目的分析多发性骨髓瘤肾脏损害的临床特征及其发生的相关因素.方法对多发性骨髓瘤患者肾脏损害的临床表现及实验室检查进行统计学分析.结果肾脏损害的发生率为39.1%(18/46),以慢性肾功能不全最常见.骨髓浆细胞数量和尿BJP与肾功能损害之间有显著相关关系(P＜0.005;P＜0.01),贫血及多发性骨损害与肾脏损害有相关关系(P＜0.05).结论骨髓浆细胞增殖及尿链蛋白产生可能是多发性骨髓瘤肾脏损害的主要原因.     

Renal insufficiency due to light chain multiple myeloma

In 3 female patients, aged 65, 83 and 76 years, with severe renal failure, light chain multiple myeloma was diagnosed, following a substantial delay on the part of the doctors concerned. Either the diagnosis had not suspected or the serum proteins had been misinterpreted. After a while, the first two patients declined further treatment with chemotherapy and haemodialysis, and subsequently died. The third patient attained a creatinine clearance of 20 ml/min and was subsequently treated for the multiple myeloma in the outpatients department. The absence of a paraprotein peak in the serum does not exclude the possibility of a multiple myeloma. In the case of light chain disease, the gammaglobulin region is, in fact, often empty. Treatment of multiple myeloma consists of a rapid rehydration and forced diuresis; the usefulness of plasmapheresis has not been demonstrated.     

Treatment of immune nephropathies with high doses of immunoglobulins

The present study presents the results from the application of high doses of gamma-globulin in the treatment of immune (idiopathic and satellite) glomerulopathies. MATERIALS AND METHODS: Twenty patients were treated. Of these 12 were with primary chronic glomerulonephritis, 7--with lupus nephritis and 1--with renal amyloidosis. All diagnoses were verified through a renal puncture biopsy. The following therapeutic scheme was used--85 mg/kg/body weight of gamma-globulin was applied intravenously three times a day every other day till reaching a total course dose of 250 mg/kg/body weight. All patients presented with nephrotic syndrome following conventional treatment with corticosteroids, anticoagulants and anti-aggregants. The blood cell count, the serum creatinine, creatinine clearance, 24 h diuresis and level of proteinuria were monitored. RESULTS AND DISCUSSION: 14 of the patients showed a complete clinical and laboratory remission. Four of them got an incomplete remission with a proteinuria of 2 g/24 h. No positive effect from the treatment was observed in 2 of the patients. All patients with lupus nephritis were influenced positively to a certain extent by the treatment applied. No serious side effects leading to therapy interruption were observed. CONCLUSIONS: 1. The treatment with high doses of immunoglobulin is a good alternative to the pulse immunosuppressive treatment of patients with idiopathic and lupus nephritides, manifested with a nephrotic syndrome and unaffected by a previous conventional immunosuppressive and anticoagulant therapy. 2. The results from the treatment with high doses of immunoglobulin are more pronounced in patients with lupus nephritides, which in turn raises the possibility for an earlier reduction of corticosteroid therapy and avoidance of its side effects. 3. Immunoglobulin therapy is an alternative in the management of nephrotic symptoms in cases with chronic renal failure where an immunosuppressive treatment is irrelevant.     

老年肾病综合征120例临床和病理特点

目的探讨、分析老年肾病综合征（NS）的临床与肾病理特点。方法回顾性分析2008年1月~2010年12月某院〉60岁120例老年NS患者的临床表现和肾活检病理诊断类型及其之间的关系。结果男性75例,女性45例,平均年龄（69.9±5.1）岁。120例NS患者中合并肾炎综合征有56例（46.7%）,合并的其他主要疾病有高血压（50例）、慢性肾病（34例）、2型糖尿病（23例）、冠心病（19例）、急性肾损伤（10例）。肾活检病理诊断中膜性肾病62例（51.7%）;其余分别为局灶节段性肾小球硬化症11例、系膜增殖性肾炎9例、IgA肾病8例、微小病变7例、糖尿病肾病5例、糖尿病肾病合并膜性肾病2例、淀粉样变肾病3例、紫癜性肾炎3例、肾小球轻微病变2例、ANCA相关性肾炎2例、多发性骨髓瘤肾损害、慢性间质性肾炎、狼疮性肾炎各1例。结论老年人发生NS临床表现与年轻患者显著不同,老年NS的病理改变仍以膜性肾病为主,存在多种继发因素。     

多发性骨髓瘤肾损害的血液净化治疗

骨髓瘤肾病是多发性骨髓瘤（MM）最常见和严重的并发症。治疗该病的关键是降低血浆轻链蛋白浓度,改善半数以上骨髓瘤肾衰患者的肾功能,从而改善MM患者的预后。目前随着对MM认识的进展,骨髓瘤肾病的合理治疗引起重视和讨论。该文主要从血液净化治疗骨髓瘤肾病的必要性、有效性、临床治疗经验、选用合理治疗方案以及治疗前景等方面进行综述。