肝脏轻链沉积病与轻链型淀粉样变性的临床病理特征

目的 探讨轻链沉积病(light chain deposition disease,LCDD)和轻链型淀粉样变性(light chain amyloidosis,AL)累及肝脏的临床病理特征及鉴别诊断.方法 回顾性分析北京佑安医院2012-2016年行肝穿刺活体组织检查,光镜初步诊断为肝淀粉样变的8例患者资料,进一步行刚果红染色、偏振光显微镜观察和轻链蛋白κ、λ的免疫组化检测,并分析其临床病理特点.结果 8例怀疑肝淀粉样变的患者均为中老年男性,临床表现为肝脏肿大,γ-谷氨酰转肽酶和碱性磷酸酶升高为主的肝功能异常,以及不同程度的蛋白尿,其中6例证实为AL,2例为LCDD.6例AL刚果红染色肝窦内呈不同程度阳性,2例伴血管壁阳性,其中4例为轻链蛋白κ沉积,2例为轻链蛋白λ沉积.2例LCDD刚果红染色均阴性,且均为轻链蛋白λ沉积.结论 以肝脏受累为突出表现的LCDD和AL,临床表现缺乏特异性,与肝脏原发疾病不易鉴别,本病确诊依赖刚果红染色及轻链蛋白检测,临床怀疑肝淀粉样病变时应尽早行肝穿刺活检以明确诊断.     

肾淀粉样变的电镜观察

目的 探讨肾淀粉样变(amyloidsis，AL)的超微结构特点及电镜在其诊断中的作用。方法 对我室近两年来接收的肾活检病例的电镜资料进行系统的回顾，疑为肾AL的病例加做刚果红染色。结果 6例肾AL均以中老年为主，临床主要表现为肾病综合征。电镜下肾小球系膜区轻度或未见增生。6例患者均可在系膜区发现节段性的淀粉样纤维分布，纤维直径8～10nm。束状淀粉纤维可在肾小球基底膜(GBM)外侧沉积形成“钉”状突起结构，突起可呈节段分布或融合成片。刚果红染色均阳性。结论 当电镜下发现肾小球系膜区及／或GBM淀粉样纤维沉积(尤其GBM外侧有淀粉沉积)时，结合临床表现，应高度怀疑淀粉样变，此时应加做光镜刚果红染色进一步确诊。     

轻链沉积病合并肾脏损害的临床特点及预后分析

目的 分析轻链沉积病(LCDD)的临床特点及预后情况.方法 回顾性分析西京医院2015-2020年收治的经肾活检证实的LCDD患者的其临床资料、肾脏病理类型、治疗及预后情况.结果 共纳入13例患者,男女比例为3.3:1.0,年龄53.77(36.00～68.00)岁.临床表现为肾病综合征范围蛋白尿(46.1％)、肾功能不全(76.9％)、高血压(84.6％).30.8％合并多发性骨髓瘤.血清游离轻链检测显示,免疫固定电泳阳性率分别为84.6％.光镜下可见弥漫性肾小管基底膜增厚(100.0％)、结节性肾小球硬化(84.6％),荧光下肾小管基底膜可见线性轻链限制性染色(κ染色阳性10例,λ染色阳性3例),电镜下均可见肾小管基底膜外和(或)肾小球基底膜内可见粉末状电子致密物沉积.13例患者,除1例起病时已透析外,8例接受了以硼替佐米为基础的治疗方案,4例给予其他治疗.平均随访(27.3±17.76)月,中位肾脏存活率为5.5年;1年、3年的肾存活率分别为67％、54％,以硼替佐米为基础的治疗,与其他治疗相比,1年肾脏存活率明显升高(87％vs.25％,P=0.04).结论 基于硼替佐米的方案治疗LCDD可获得持续的血液学反应,明显改善肾脏存活率.     

轻链沉积病合并肾脏损害的临床特点及预后分析

目的 分析轻链沉积病(LCDD)的临床特点及预后情况.方法 回顾性分析西京医院2015-2020年收治的经肾活检证实的LCDD患者的其临床资料、肾脏病理类型、治疗及预后情况.结果 共纳入13例患者,男女比例为3.3:1.0,年龄53.77(36.00～68.00)岁.临床表现为肾病综合征范围蛋白尿(46.1％)、肾功能不全(76.9％)、高血压(84.6％).30.8％合并多发性骨髓瘤.血清游离轻链检测显示,免疫固定电泳阳性率分别为84.6％.光镜下可见弥漫性肾小管基底膜增厚(100.0％)、结节性肾小球硬化(84.6％),荧光下肾小管基底膜可见线性轻链限制性染色(κ染色阳性10例,λ染色阳性3例),电镜下均可见肾小管基底膜外和(或)肾小球基底膜内可见粉末状电子致密物沉积.13例患者,除1例起病时已透析外,8例接受了以硼替佐米为基础的治疗方案,4例给予其他治疗.平均随访(27.3±17.76)月,中位肾脏存活率为5.5年;1年、3年的肾存活率分别为67％、54％,以硼替佐米为基础的治疗,与其他治疗相比,1年肾脏存活率明显升高(87％vs.25％,P=0.04).结论 基于硼替佐米的方案治疗LCDD可获得持续的血液学反应,明显改善肾脏存活率.     

免疫球蛋白及轻链检测在多发性骨髓瘤诊断中的临床意义

目的　探讨免疫球蛋白及轻链检测在多发性骨髓瘤诊断中的临床意义。方法　对 4 5例多发性骨髓瘤患者采用速率散射比浊法检测免疫球蛋白及轻链。结果　 ( 1) 2 6例为IgG型 ,其中IgGκ型 17例 ,IgGλ型 9例 ;11例为IgA型 ,其中IgAκ型 8例 ,IgAλ型 3例 ;3例为IgM型均为IgMλ型 ;5例为轻链型 ,其中κ型轻链 4例、λ型轻链 1例 ;( 2 )IgG型血清免疫球蛋白IgG、IgA型血清免疫球蛋白IgA和IgM型血清免疫球蛋白IgM的检测结果与正常对照组比较 ,均有显著性差异 (P <0 .0 1 ;( 3)IgGκ型、IgGλ型、IgAκ型、IgAλ型、IgMλ型、LCκ型的血、尿液κ、λ轻链检测结果与正常对照组比较 ,均有显著性差异 (P <0 .0 1 。结论　血清免疫球蛋白及血、尿液轻链的检测对多发性骨髓瘤患者的早期诊断和鉴别诊断有重要意义     

轻链和免疫球蛋白检测对多发性骨髓瘤的诊断意义

目的探讨轻链和免疫球蛋白检测在多发性骨髓瘤(Multiple myeloma,MM)诊断中的临床意义。方法选择53例MM患者以及30例正常对照者,用免疫比浊法测定血清免疫球蛋白(Ig A、IgG、IgM)、β2-MG和κ、λ轻链,计算κ/λ比值,同时检测血清尿素氮(UREA)和肌酐(CREA)。对检测结果进行统计学分析。结果在53例MM患者中,以IgG型MM患者最多,占54.72%,其中以IgGκ型为主。各型MM患者及正常对照组κ、λ及κ/λ比值结果比较,IgGκ型κ/λ比值明显升高,而IgGλ型κ/λ明显降低,与对照组比较,差异均有统计学意义(P均0.05)。轻链型MM和IgG型MM的IgG二者比较差异有统计学意义(P0.05)。结论血清轻链和免疫球蛋白及κ/λ比值的测定可为MM的诊断提供较好的临床依据。     

肾病综合征患者尿TRF,MA和IgG及轻链(κ,λ)的检测及其临床意义

目的 探讨肾病综合征(nephrotic syndrome,NS)患者尿微量白蛋白(MA),转铁蛋白(TRF),IgG及轻链(κ,λ)含量的变化及临床意义.方法 采用速率散射比浊法检测50例肾病综合征患者、25例肾小球肾炎患者及40例健康者尿MA,TRF,IgG及轻链(κ,λ)的含量.结果 ①肾病综合征组尿MA,TRF,IgG及轻链κ,λ含量显著高于肾小球肾炎组和正常对照组(P＜0.01);肾小球肾炎组尿MA,TRF,IgG及κ轻链含量显著高于正常对照组(P＜0.01),但轻链λ的含量与正常对照组差异无显著性(P＞0.05).②肾病综合征患者予激素治疗后尿MA,TRF,IgG及轻链κ,λ含量均显著降低,与治疗前比较差异有显著性(P＜0.01).结论 检测尿TRF,MA和IgG及轻链(κ,λ)的含量对肾病综合征患者诊断及疗效观察有重要的临床意义.     

κ及λ轻链测定在多发性骨髓瘤诊断中的应用

目的：寻求准确，可靠的免疫球蛋白及κ和λ轻链测定方法，提高多发性骨髓瘤分型和鉴别诊断水平。     

尿游离轻链测定对糖尿病早期肾损害的诊断价值

目的:探讨尿游离轻链测定对糖尿病(DM)患者早期肾脏损害的诊断价值.方法:以速率散射比 浊法测定79例DM患者和35例健康体检者尿液中游离轻链(κ、λ)和α1微球蛋白(α1-MG)水平,并对检测结果进行统计分析.结果:DM组尿轻链κ、λ和α1-MG水平显著高于对照组(P＜0.01),糖尿病微量白蛋白尿组κ、λ和α1-MG水平显著高于糖尿病正常白蛋白尿组及对照组(P＜0.01),DM患者大部分同时存在尿κ和λ的升高,κ/λ值则与对照组差异无显著性(P＞0.05);随着病程的增加,DM患者尿游离轻链和α1-MG水平及其阳性检出率不断升高;DM患者尿轻链水平和α1-MG呈显著正相关(P＜ 0.01),两种方法对早期糖尿病肾病(DN)的诊断结果无差别(P＞0.5).结论:尿轻链κ、λ测定对早期DN的发现有重要意义,可作为DM患者肾脏损害的早期监测指标.     

轻链检测在慢性肾脏病中的应用评估

目的 评估慢性肾脏病(CKD)患者在不同分期下,血总轻链(sTLC)、尿总轻链(uTLC)及血游离轻链(sFLC)水平差异及其与肾功能指标的相关性;探讨各轻链指标在CKD患者分期中的预测价值。方法 回顾性分析292例CKD患者,排除浆细胞疾病、急性肾损伤、肿瘤性疾病等。根据估算肾小球滤过率(eGFR)将CKD患者分为CKD1～5期组。检测CKD患者sTLC、uTLC、sFLC及相应生化指标,比较各组指标间差异及相关性;采用受试者应用工作曲线(ROC曲线),以CKD1～2期合并为对照组,CKD3～5期合并为病例组,分析各轻链指标在CKD分期中的预测价值。结果 CKD 1～5期多组间比较显示,sTLCκ、sTLCλ、sTLCκ/λ、sFLCκ/λ差异无统计学意义;而sFLCκ、sFLCλ、uTLCκ、uTLCλ差异有统计学意义(P<0.05),且随着CKD分期期次的增高而增高。sFLCκ、sFLCλ与肌酐(Scr)、尿素氮(BUN)、eGFR的相关系数高于uTLCκ、uTLCλ(P<0.001);sTLCκ、sTLCλ、sTLCκ/λ、sFLCκ/λ与肾功能指标相关系数低(P&...     

肾穿刺的病理分析及免疫学模式探讨

用光学、免疫荧光及透射电子显微镜对72例肾炎患者进行了肾穿刺的前瞻性研究。结果发现肾小球毛细血管丛系膜细胞不同程度的增生;用电镜观察,见上皮细胞足突融合是多数肾炎的非特异性病理特征。在相同病因和机理支配下产生的沉积物既可以是线型的,也可以是颗粒状的。因此,免疫荧光线型沉积不仅是在抗基底膜型肾小球肾炎中出现,而且可在其他型的肾小球肾炎中查见。     

触须样免疫性肾小球病的临床病理观察

目的 了解国内触须样免疫性肾小球病（ｉｍｍｕｎｏｔａｃｔｏｉｄ ｇｌｏｍｅｒｕｌｏｐａｔｈｙ， ＩＴ）的发病及其临床病理特点。方法应用电子显微镜观察了北京医科大学第一医院肾内科１９９２－１９９５年所做肾活检６００例患者,其中３例符合ＩＴ，并通过临床分析，光学显微镜，免疫荧光检查，刚果红染色及图像分析技术等，除外了淀粉样变性病，纤维样肾小球病及其他系统性疾病。结果３例患者ＩＴ的超微病理特点：在肾小球不同部位及电子致密物中可见大量微管状纤维（直径３５－４７ｎｍ），并伴有直径约２０ｎｍ的紊乱排列的纤维样物质沉积，刚果红染色阴性，患者为中青年男性，有蛋白尿，镜下血尿及高血压，２例出现肾功能不全。结论（１）ＩＴ为少见肾病，我国也有该病发生；（２）与国外病例相比，该３例发病年龄较轻，预后较差；（３）病变中微管状和纤维样物质同时存在，说明ＩＴ和纤维样肾小球病可能为同一疾病的两种类型。     

A clinicopathological study of Alport syndrome and detection of type IV collagen chains in Alport patients

OBJECTIVE To summarize the clinical and pathological findings of Alport syndrome (AS), detect the distribution of type IV collagen within basement membrane of patients with AS and evaluate the diagnostic value of indirect immunofluorescence (iIF) study of type IV collagen in AS.

METHODS Fourteen patients belonging to 12 families were collected from January 1990 to June 1996. The clinical examinations include biochemical examination, audiometry and ocular examination. IIF technique was used to detect the location of chains of type IV collagen in 6 renal and 5 skin specimens from 8 Alport patients.

RESULTS Among fourteen patients, 11 were male and 3 female (mean age 29.4 years). Microscopic hematuria was found in 13 patients, and recurrent gross hematuria in 7. All had proteinuria. Three patients presented nephrotic syndrome. Slowly progressive renal failure occurred in 10 of 11 males (11-39 years) and 1 female (40 years). Sensorineural deafness was observed in 9 patients particularly high frequency sound. Anterior lenticonus were presented in 2. Five families transmitted as X-linked dominant (XD) trait and 3 autosomal dominant, 3 autosomal recessive inheritance. In 7 renal biopsies, the findings by light microscopy mostly revealed focal and segmental sclerosis glomerulonephritis (4/7). The results of IF were negative in 4. Ultrastructural studies showed variable thickening, thinning of glomerular basement membrane (GBM) in 7 specimens with lamellation and basket wearing of GBM in 1. Using the iIF technique, the alpha 3, 4, 5 (IV) chains were observed to be absent within both GBM and EBM of 4 male XD-AS patients. Six patients were treated with hemodialysis, 2/6 with transplantation.

CONCLUSIONS Alport syndrome (AS) is a heterogeneous hereditary disease characterized by progressive hematuric nephritis with or without sensorineural hearing loss and ocular defects. Ultrastructural alterations of GBM are helpful to the diagnosis of AS. IIF study suggests that type IV collagen in basement membrane of AS was abnormal and iIF study of type IV collagen chains distribution is useful for confirming the diagnosis of AS.

     

A clinicopathological study of Alport syndrome and detection of type Ⅳ collagen chains in Alport patients

Objective To summarize the clinical and pathological findings of Alport syndrome (AS), detect the distribution of type Ⅳ collagen within basement membrane of patients with AS and evaluate the diagnostic value of indirect immunofluorescence (iIF) study of type Ⅳ collagen in AS.Methods Fourteen patients belonging to 12 families were collected from January 1990 to June 1996. The clinical examinations include biochemical examination, audiometry and ocular examination. IIF technique was used to detect the location of chains of type Ⅳ collagen in 6 renal and 5 skin specimens from 8 Alport patients.Results Among fourteen patients, 11 were male and 3 female (mean age 29.4 years). Microscopic hematuria was found in 13 patients, and recurrent gross hematuria in 7. All had proteinuria. Three patients presented nephrotic syndrome. Slowly progressive renal failure occured in 10 of 11 males (11-39 years) and 1 female (40 years). Sensorineural deafness was observed in 9 patients particularly high frequency sound. Anterior lenticonus were presented in 2. Five families transmitted as X-linked dominant (XD) trait and 3 autosomal dominant, 3 autosomal reccessive inheritance. In 7 renal biopsies, the findings by light microscopy mostly revealed focal and segmental sclerosis glomerulonephritis (4/7). The results of IF were negative in 4. Ultrastructural studies showed variable thicking, thinning of glomerular basement membrane (GBM) in 7 specimens with lamellation and basket wearing of GBM in 1. Using the iIF technique, the α 3, 4, 5 (Ⅳ) chains were observed to be absent within both GBM and EBM of 4 male XD-AS patients. Six patients were treated with hemodialysis, 2/6 with transplantation.Conclusion Alport syndrome (AS) is a heterogeneous hereditary disease characterized by progressive hematuric nephritis with or without sensorineural hearing loss and ocular defects. Ultrastructural alterations of GBM are helpful to the diagnosis of AS. IIF study suggests that type Ⅳ collagen in basement membrane of AS was abnormal and iIF study of type Ⅳ collagen chains distribution is useful for confirming the diagnosis of AS.     

A case of renal γ2 heavy-chain deposition disease accompanied by rapid progressive renal failure

Background

The recently described heavy-chain deposition disease (HCDD) is a comparatively rare monoclonal immunoglobulin disorder characterized histopathologically by glomerular and tubular basement membrane deposition of nonamyloidotic monoclonal heavy chains without associated light chains.

Method

We have described a case of γ2-HCDD presenting with proteinuria, microhematuria, severe hypertension, and rapidly progressive renal failure, which serum creatinine level was only 1.52 mg/dL in early stage HCDD, and the clinicopathologic features of this case have been compared with other reported cases of γ2-HCDD.

Results

Renal biopsy disclosed nodular sclerosing glomerulopathy. Immunofluorescence analysis revealed IgG2 (2+) heavy chain and C3 (+) in the mesangium and along the capillary walls and tubular basement membranes without IgA, IgM, κ and λ light chains. Electron microscopy revealed electron-dense deposits along the glomerular and tubular basement membranes as well as in the mesangium. Moreover, regardless of therapy, the condition of the patient progressively deteriorated, with less than 3 months of renal survival.

Conclusion

Rapid progressive renal failure was a common feature in both cases of γ2-HCDD. We propose that a possible link exists between prognosis of renal HCDD and the subclass of heavy chain deposited in the kidney.     

Localized AL amyloidosis: A suicidal neoplasm?

Abstract

Although AL amyloidosis usually is a systemic disease, strictly localized AL deposits are not exceptionally rare. Such case reports form a considerable body of published articles. Although both AL amyloidosis types are formed from an N-terminal segment of a monoclonal immunoglobulin light chain, a typical localized AL amyloid differs from the systemic counterpart by the morphological appearance of the amyloid, and presence of clonal plasma cells and of giant cells. In this article it is pointed out that localized AL amyloidosis (‘amyloidoma') represents a true plasma cell neoplasm and not a pseudotumor. The pathogenesis of localized AL amyloidosis may differ from that of the systemic type, a suggestion underlined by the fact that localized AL amyloidosis of kappa type is as common as that of lambda origin, in contrast to the systemic form where lambda chains constitute the overwhelming majority of cases. It is suggested that oligomeric assemblies of the produced immunoglobulin light chain are toxic to plasma cells, which in this way commit suicide.     

薄盖灵芝注射液对家兔膜性肾小球肾炎影响的病理形态观察

借助光电镜技术,观察了薄盖灵芝注射液对Border膜性肾小球肾炎家兔模型的免疫荧光,显微和超微结构的影响。结果表明,薄盖灵芝注射液能减弱免疫荧光强度;减轻。膜性病变”;减少“钉突”和上皮下电子致密沉积物形成,并使肾小球基底膜明显变薄。     

56例肾淀粉样变性的病理分型及临床分析

目的 分析肾淀粉样变性的组织学特点及临床表现,提高对该病的诊断水平.方法 回顾性分析复旦大学基础医学院病理学系2007年1月至2016年7月肾活检病例中确诊的56例肾淀粉样变性,经免疫染色检测肾组织中免疫球蛋白轻链κ、λ及淀粉样蛋白A(amyloid A,AA)的表达,并分析病理形态学特点及临床表现.结果 56例肾淀粉...     

CLINICAL PATHOLOGICAL FEATURE OF EARLY TONGUE AMYLOIDOSIS

AMYLOIDOSIS (AL) is known as a disease thataffects almost all organs, and may especiallycause widespead damage to the tongue·1For thevariety of protein species involved and the wide spectrumof possible clinical presentations, tongue AL is frequentlyoverl…     

家兔实验性膜性肾小球肾炎的光镜与电镜图象立体学定量分析

采用Border膜性肾小球肾炎模型作为实验组,另设正常对照组,从光镜与电镜图象立体学定量角度观察分析膜性肾小球肾炎的病理变化。结果表明:实验组上皮电子致密沉积物及肾小球各定量参数与对照组比较有显著和极显著差异性(P<0.05和P<0.001)。实验组第8周新月体(或环状体)的体密度为17.39％。对照组与实验组基底膜厚度分别为168nm和627nm(P<0.001)。