Renal transplantation in amyloidosis: effects of HLA matching and donor type on recurrence of primary disease

The aim of this study is to evaluate the effect of HLA-matching and donor type on recurrence of amyloidosis after renal transplantation. The study includes 30 patients with systemic amyloidosis who received kidney transplants between 1985 and 2001. Donor source and HLA tissue typing of the donor and recipient were evaluated in each case. Of the 30 patients, 20 developed a recurrence of amyloidosis in their allografts, as confirmed by biopsy. The time from transplantation to diagnosis of amyloidosis in the graft ranged from 18 months to 10 years. Of the 20 patients with recurrence, 18 had received their grafts from living related donors (LRDs), and 2 had received their grafts from cadaveric donors (P<0.01). There was a strong correlation between amyloidosis recurrence and degree of HLA-DR matching (P<0.05). Furthermore, in the recipients of LRD grafts, the risk of amyloidosis recurrence was much higher if the donor-recipient pair were HLA-identical than if they were not perfectly matched (P<0.01). The incidence of amyloidosis recurrence in our patients was significantly higher than the rates reported for other series. Most of the cases in previous reports involved cadaveric grafts. The higher rate of amyloidosis recurrence in our patients may be explained by the high proportion of LRD grafts and by genetic susceptibility.     

Laryngeal plasmacytoma presenting as amyloid tumour: a case report

Laryngeal amyloidosis can be secondary to an underlying lymphoid neoplastic process and in view of this concept; the cases of localized laryngeal amyloidosis should be carefully examined and investigated for the presence of a lymphomatous process. The study design is case report. We report the case of a 64-year-old man with progressive hoarseness. A biopsy showed histological findings consistent with an extramedullary plasmacytoma associated with localized amyloidosis involving the right hemilarynx (ventricular band, arytenoids and true cord). Immunohistochemical studies showed that the tumour cells of the plasmacytoma were monoclonal (lambda-restricted). PCR analysis of the IgH gene demonstrated a clonal band confirming B-cell clonality. The amyloid deposits were also shown to be reactive with lambda immunoglobulin light chain, suggesting the pathogenetic relationship between the plasmacytoma and amyloid deposition in the larynx. There was no other evidence of malignancy or amyloidosis elsewhere. The majority of the cases reported of amyloid deposition with plasmacytoma, the lesions were found in the nasopharynx, in contrast to our case in which the lesions were sited in the larynx and with the peculiarity of being multiples. Moreover, amyloid and plasmacytoma were clearly delimitated and the amyloid tissue was more extensive than the tumour tissue. This case supports the concept that localized laryngeal amyloidosis may be a manifestation of low-grade B-cell neoplasms.     

一个遗传性玻璃体淀粉样变性家系TTR基因的突变检测

目的 对1个遗传性玻璃体淀粉样变性家系进行致病基因分析.方法 采集该家系4个成员(包括临床确诊患者3例,无症状者1例)的外周静脉血,提取基因组DNA.PCR方法扩增TTR基因的4个外显子,产物直接测序进行基因突变检测,同时选择150名无亲缘关系的正常对照.结果 该家系的4例受检者中均检测到TTR基因第3外显子第103位密码子发生了G＞C(Gly103Arg)杂合突变,而150名正常对照中未发现相同的突变.结论 TTR基因Gly103Arg杂合突变可能与该家系遗传性玻璃体淀粉样变性的发病有关.     

Heart involvement in rheumatoid arthritis: Multimodality imaging and the emerging role of cardiac magnetic resonance

Objectives

Patients with rheumatoid arthritis (RA) exhibit a high risk of cardiovascular disease (CVD). CVD in RA can present in many guises, commonly detected at a subclinical level only.

Methods

Modern imaging modalities that allow the noninvasive assessment of myocardial performance and are able to identify cardiac abnormalities in early asymptomatic stages may be useful tools in terms of screening, diagnostic evaluation, and risk stratification in RA.

Results

The currently used imaging techniques are echocardiography, single-photon emission computed tomography (SPECT), and cardiac magnetic resonance (CMR). Between them, echocardiography provides information about cardiac function, valves, and perfusion; SPECT provides information about myocardial perfusion and carries a high amount of radiation; and CMR—the most promising imaging modality—evaluates myocardial function, inflammation, microvascular dysfunction, valvular disease, perfusion, and presence of scar. Depending on availability, expertise, and clinical queries, “right technique should be applied for the right patient at the right time.”

Conclusions

In this review, we present a short overview of CVD in RA focusing on the clinical implication of multimodality imaging and mainly on the evolving role of CMR in identifying high-risk patients who could benefit from prevention strategies and early specific treatment targeting the heart. Advantages and disadvantages of each imaging technique in the evaluation of RA are discussed.     

原发淀粉样变病的胸部表现(附九例报告)

目的　分析原发淀粉样变病累及胸部的影像学表现。方法　 5例局限性病变患者均行X线胸片、气管分叉体层及支气管镜检查 ,其中 3例做了CT检查 ;4例全身性病变患者行X线胸片、CT及超声心动图检查。 2例经尸检 ,7例经全身多部位组织活检证实。结果　 5例局限性病变患者均有气管支气管树的狭窄或闭塞 ,其中 2例分别合并左舌叶与右上叶阻塞性肺不张 ;4例全身性病变患者中肺间质病变 3例 ,胸膜增厚 4例 ,胸腔积液 4例 ,室间隔与左心室肌增厚 3例 ,心包积液 1例。结论　局限于气管支气管树的原发淀粉样变病具有一定的影像特点 ,而全身性原发淀粉样变病累及胸部的有关影像学表现缺乏特征性 ,诊断依靠病理活检     

Ultrastructural immunolabelling of amyloid fibrils in acquired and hereditary amyloid neuropathies

Both acquired and familial amyloid neuropathies carry a poor prognosis. In addition, amyloid is sometimes difficult to visualise in nerve biopsy specimens, and the pathogenesis of nerve lesions is still a matter of controversy. In order to learn more on the subject, we studied nerve specimens from seven patients with proven amyloid neuropathy by ultrastructural immunocytochemistry in order to better understand their pathogeny and to evaluate the reliability of the method for detection of amyloid antigens in the endoneurium. An indirect immunolabelling technique using protein A-gold complex (pA-g) was applied. Polyclonal antisera against human IgG, IgM, lambda and kappa light chains and prealbumin were assayed. Amyloid fibrils were labelled in six of seven cases: in four cases with anti-transthyretin (TTR) antibodies and in two with anti-lambda light chain antibodies. The type of immunolabelling correlated with the biochemical type of the amyloidosis as defined by TTR gene analysis and serum immunoelectrophoresis. The amyloid fibrils and gold labelling were always located in the endoneurial space. No intracellular deposit or labelling was found. The immunolabelling was highly specific, gold particles being detected only near to amyloid fibrils with no background gold labelling. Ultrastructural immunolabelling with pA-g could be used for detection of amyloid in progressive axonal neuropathy of unknown origin, with important therapeutic implications.     

Amyloid-β oligomer synaptotoxicity is mimicked by oligomers of the model protein HypF-N

Protein misfolded oligomers are thought to be the primary pathogenic species in many protein deposition diseases. Oligomers by the amyloid-β peptide play a central role in Alzheimer's disease pathogenesis, being implicated in synaptic dysfunction. Here we show that the oligomers formed by a protein that has no link with human disease, namely the N-terminal domain of HypF from Escherichia coli (HypF-N), are also synaptotoxic. HypF-N oligomers were found to (i) colocalize with post-synaptic densities in primary rat hippocampal neurons; (ii) induce impairment of long-term potentiation in rat hippocampal slices; and (iii) impair spatial learning of rats in the Morris Water Maze test. By contrast, the native protein and control nontoxic oligomers had none of such effects. These results raise the importance of using HypF-N oligomers as a valid tool to investigate the pathogenesis of Alzheimer's disease, with advantages over other systems for their stability, reproducibility, and costs. The results also suggest that, in the context of a compromised protein homeostasis resulting from aggregation of the amyloid β peptide, a number of oligomeric species sharing common synaptotoxic activity can arise and cooperate in the pathogenesis of the disease.     

Plasmapheresis and Paraproteinemia: Cryoprotein-Induced Diseases,Monoclonal Gammopathy,Waldenström's Macroglobulinemia,Hyperviscosity Syndrome,Multiple Myeloma,Light Chain Disease,and Amyloidosis

Therapeutic plasmapheresis has been in widespread use as either a primary or adjunctive therapy in the United States since the 1960s. There are several types of plasmapheresis procedures used to treat various diseases. Plasma exchange with a centrifugal plasma separator using replacement fluid such as human albumin solution is the most widely used method in the United States. Other forms of plasmapheresis include membrane plasma separation, membrane fractionation, cryofiltration apheresis, immunoadsorption, and chemical affinity column pheresis. Therapeutic plasmapheresis has been used for the treatment of paraproteinemia to remove harmful paraproteins. Paraproteinemia is a disease classification in which abnormal or large amounts of plasma proteins such as cryoproteins or immunoglobulins are produced. In most cases, plasmapheresis is used in combination with corticosteroids and immunosuppressive drugs to prevent production of abnormal proteins or to treat the underlying disease. Cryoprotein-induced diseases, which include cryoglobulinemia, cryofibrinogenemia, and cold IgM antibody agglutinin with cryoglobulin properties, are a subclass of paraproteinemia. Other categories of paraproteinemia include monoclonal gammopathy, Waldenström's macroglobulinemia, hyperviscosity syndrome, multiple myeloma, light chain disease, and amyloidosis. Some of these diseases may be interrelated, and they may be associated with one another. In this review paper, we discuss the role of plasmapheresis in the specific classes of paraproteinemia in the United States, including our own experience.