Experimental study using heparin-immobilized adsorbent of EDA(+)fibronectin.

EDA(+)fibronectin, which might participate in the pathogenesis and/or progress of immune diseases, is efficiently removed from plasma by cryofiltration; however, cryofiltration removes not only EDA(+)fibronectin, but also other proteins. We thus developed a new adsorbent by using its high affinity with heparin. The purpose of this study was to evaluate the efficacy of the adsorbent of EDA(+)fibronectin (OHC-20) in experimental arthritis. The experimental arthritis was induced by injection of 0.5 mg of Mycobacterium butyricum in Lewis rats. Rats were divided into 4 groups; 1 nontreatment group, and 3 treatment groups. Adsorption therapy in treatment groups was performed three times: on Days 1, 3, and 5 in Group A; Days 7, 9, and 11 in Group B; and Days 13, 15, and 17 in Group C. The walking postures of rats improved from dragging to walking on tiptoe, and the increase of hind-foot volume was suppressed in Groups B and C. We conclude that heparin-immobilized adsorbent might be promising for immune diseases.     

Antibodies reacting with the antigens of the human immunodeficiency virus in systemic lupus erythematosus

A study was made of the level of anti-HTLV-111 using an enzyme immunoassay (Emzygnost-anti-HTLV-111) in 75 donors and 143 patients with various diseases including SLE (57), rheumatoid arthritis (9), Sj?gren's disease (3), Bekhterev's disease (2), polymyositis (2), dilatation cardiomyopathy (30), and acute lymphocytic leukemia (40). Anti-HTLV-111 were detected in 26 SLE patients and in one patient with polymyositis. A study of positive sera using immunoblotting showed no interaction with virus antigens. A conclusion was made that the detection of anti-HTLV-111 in systemic rheumatoid diseases was a false-positive result.     

Immunomodulation in transplant patients by cryofiltration.

Cryofiltration was applied to major ABO incompatible bone marrow transplant (BMT), renal transplant, and chronic renal rejection cases. The anti-ABO titers IgM and IgG pretreatment by cryofiltration were x64 and x8 in a major ABO incompatible BMT patient. After treatments, they were decreased to x16 and x2, respectively. BMT was performed successfully. In a case of ABO major incompatible renal transplant, anti-A-IgM before cryofiltration treatment was x128, and CH50 was 26.5. Three treatments were performed. As a result, the anti-A-IgM and CH50 levels were decreased to x4 and under 10. After renal transplantation, antibodies appeared again, but because the creatinine level was normal, cryofiltration was not performed again. Five cases of chronic rejection of renal transplants were treated by cryofiltration. They remained hemodialysis (HD) free for an average of 17.4 months, and the longest duration was 32 months. Cryofiltration is a good treatment for extracorporeal immunomodulation in transplantation.     

风湿病中关节炎与支原体感染的关系研究

目的　应用套式聚合酶链反应 (nPCR)检测技术探讨风湿病中关节炎与支原体感染的关系。方法　对 2 6例类风湿关节炎 (RA) ,2 4例反应性关节炎 (ReA)、3例系统性红斑狼疮 (SLE)、1例干燥综合症 (SS)、1例骨关节炎 (OA)、1例未分化结缔组织病 (UCTD)、3例强直性脊柱炎 (AS)病人关节液用nPCR方法联合检测支原体 :解脲脲原体 (Uu)、人型支原体 (Mh)、发酵支原体 (Mf)、关节炎支原体 (Mar)。结果　 2 6例RA患者中 ,2例Uu阳性、1例Mh阳性、1例Mar阳性。 2 4例ReA患者中 ,2例Uu阳性、2例Mh阳性。 3例SLE患者中 ,1例Uu阳性。2例Mh阳性 ,1例SS患者Mh阳性。结论　风湿病中关节炎与支原体感染有密切关系 ,支原体感染可能是风湿病发病的一个重要因素之一。     

血清葡萄糖-6-磷酸异构酶与自身免疫性疾病相关性研究

目的探讨血清葡萄糖-6-磷酸异构酶(GPI)水平与各种自身免疫性疾病(AID)的关系。方法比较正常对照和各种AID确诊病例的血清GPI浓度,分析GPI在各种AID中的检测价值。结果类风湿性关节炎(RA)组的GPI浓度和阳性率都显著高于其他AID组和正常对照组(P<0.001),系统性红斑狼疮(SLE)组、干燥综合征(SS)组、多发性肌炎(PM)组、进行性系统性硬皮病(SSC)组和强直性脊柱炎(AS)组GPI的阳性率均在25%以下,显著低于RA组的阳性率(71.0%)。结论在各种AID中,RA组血清中GPI升高最明显。血清GPI检测可作为RA的诊断指标。如果GPI和类风湿因子(RF)联合检测,将对RA的诊断具有较高价值。     

4种结缔组织病患者血管内皮细胞生长因子检测的分析

目的检测4种结缔组织病患者血清中血管内皮细胞生长因子(VEGF)水平,并探讨其意义。方法115例患者中,类风湿关节炎(RA)40例,系统性红斑狼疮(SLE)30例,多发性肌炎/皮肌炎(PM/DM)25例,系统性硬化症(SSc)20例,正常对照30例,采用酶联免疫吸附试验(ELISA)方法检测了血清中的VEGF(ng/L)的含量。结果血清VEGF水平(单位ng/L)分别为RA558.58±348.45,SLE244.63±87.44,PM/DM355.12±258.56,SSc362.72±177.52,类风湿关节炎、系统性红斑狼疮、多发性肌炎/皮肌炎、系统性硬化症患者血清VEGF水平均明显高于正常对照(P<0.01,P<0.05)。结论血清VEGF水平的测定对结缔组织病病情监测可能具有非常重要意义。     

Glycosylation of alpha 1-acid glycoprotein in relation to duration of disease in acute and chronic infection and inflammation.

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.     

Studies with human leukocyte lysosomes. Evidence for antilysosome antibodies in lupus erythematosus and for the presence of lysosomal antigen in inflammatory diseases.

Human lysosomes were isolated from normal peripheral blood leukoyctes and characterized by electron microscopy, enzyme analysis, and assays for DNA and RNA. Stored sera from 37 unselected patients with systemic lupus erythematosus (SLE), including active and inactive, treated and untreated cases, were tested in complement fixation (CF) reactions with these lysosome preparations. 23 SLE sera exhibited positive CR reactions, as did sera from two patients with "lupoid" hepatitis. The seven SLE sera with strongest CF reactivity also demonstrated gel precipitin reactions with lysosomes. Neither CF nor precipitin reactions with lysosomes were observed with normal sera or with sera of patients with drug-induced lupus syndrome, rheumatoid arthritis (RA), polymyositis, or autoimmune hemolytic anemia. By several criteria the antilysosome CF and precipitin reactions of SLE sera cound not be attributed to antibody to DNA, RNA, or other intracellular organelles. The lysosomal component reactive with SLE sera in CF assays was sedimentable at high speed and is presumably membrane associated. The CF activity of two representative SLE sera was associated with IgG globulins by Sephadex filtration. A search for lysosomal antigen in SLE and related disorders was also made. By employing rabbit antiserum to human lysosomes in immunodiffusion, a soluble lysosomal component, apparently distinct from the sedimentable (membrane-associated) antigen described above, was identified in serum, synovial fluid, or pleural fluid from patients with SLE, RA, ankylosing spondylitis, and leukemoid reaction. An antigenically identical soluble component reactive with the rabbit antiserum could be released in vitro from intact lysosomes by repeated freeze-thaw cycles..     

自身免疫性疾病合并恶性肿瘤17例分析

目的总结自身免疫性疾病并发恶性肿瘤临床表现。方法回顾性分析1997年6月至2006年6月在我科住院的所有患者,选取其中并发恶性肿瘤的患者进行分析。结果自身免疫性疾病并发恶性肿瘤共17例,其中多发性肌炎/皮肌炎并发肿瘤9例,类风湿性关节炎并发肿瘤3例,系统性红斑狼疮并发肿瘤2例,强直性脊柱炎、银屑病关节炎、原发性小血管炎并发肿瘤各1例,恶性肿瘤包括鼻咽癌5例,乳腺癌5例,肺癌4例,肝癌、肾癌、多发性骨髓瘤各1例。经正规治疗,只有3例患者红细胞沉降率完全回复正常水平,其余14例只有轻度下降。结论自身免疫性疾病容易合并恶性肿瘤,其中以多发性肌炎、皮肌炎最易并发,对经正规治疗后红细胞沉降率无明显下降的患者要排除有无肿瘤。     

Uncontrolled trial of cryofiltration in rheumatoid arthritis

In an open trial of cryofiltration in rheumatoid arthritis at our institution, 19 patients received 464 treatments; the intensive schedule of ten treatments in 5 weeks was completed in 14 of the 19, and excellent to good clinical response was achieved in ten of these. The combined results demonstrated significant reductions in Ritchie index, morning stiffness, and 50-foot-walk time in the intensive treatment period, as well as significant increases in hand grip strengths. In the maintenance treatment period treatment frequency was individually selected and at less frequent intervals. Changes in clinical parameters were notably less. Although significant correlations were observed between the percent change in clinical parameters and the percent change in biochemical and hematological parameters, no consistent pattern was found. The favorable results of this trial and other uncontrolled trials has led to a two-center double-blind controlled trial of cryofiltration in rheumatoid arthritis that is now in progress.     

系统性红斑狼疮合并胸主动脉瘤破裂

报告1例18岁男性系统性红斑狼疮（SLE）患者，死于夹层主动脉瘤破裂。尸检显示主动脉根部至胸主动脉夹层动脉瘤，长17cm，主动脉滋养血管炎及小血管周围炎。本例与以往文献报告的类似病例共31例的临床资料及病理情况汇总分析，显示长期激素治疗可能在SLE患者主动脉瘤形成中起重要作用，动脉粥样硬化、主动脉炎、滋养动脉炎、高血压等可参与其形成。     

Backwashing procedure for on-line reuse of a plasma fractionator in cryofiltration

During membrane plasma fractionation therapy there are reported incidences of membrane plugging requiring the corrective actions of either filter replacement or backwashing (BW) in order to continue the treatment. In this preliminary study, a simple BW procedure to allow for on-line reuse of the filter (Asahi AP06M) during the treatment was evaluated to assess its efficacy and safety in cryofiltration (CF). Evaluations were carried out on two patients treated for rheumatoid arthritis. Seven tests, each using 1 L or 2 L warmed saline as a BW solution were performed to evaluate the decrease of the transmembrane pressure (TMP) between just before and after backwashing and TMP change during cryofiltration procedures between before and after backwashing. Sieving coefficients of total protein, albumin, immunoglobulins (G, M, A), fibrinogen, and rheumatoid factor were also calculated at 1,000 ml plasma volume processed. Results showed statistically significant decreases of TMP from 300 mm Hg to 70 mm Hg between just before and after both backwashing procedures, and that there were no significant changes in the TMP increase during the cryofiltration procedure between pre- and post-BW. The protein sievings were not significantly affected by BW. The use of a second liter for rinsing did not reduce the inlet pressure further suggesting that 1 L BW was adequate. The accumulated solutes did not affect significantly the effective mean pore size. The BW procedure did not affect the overall patient safety during therapy. In conclusion, this simple BW procedure using 1 L of normal saline and accomplished in approximately 11 minutes by a manual procedure proved reliable to rinse the filter and to prolong its clinical use. This procedure obviated the need for filter replacement.     

Overlapping syndrome]

Overlapping syndrome (OS) is usually used as the term of the combinations of three connective tissue diseases, i.e., systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and polymyositis (PM) or dermatomyositis (DM). OS is sometimes confused with mixed connective tissue disease (MCTD) since the definitions of the both diseases have not been established yet. Rheumatoid arthritis (RA) is a distinct disease and only exceptionally associated with the other CTD. These rare cases include destructive arthritis of SLE and PSS, multiple peripheral type of psoriatic arthritis, and arthritis associated with X-linked hypogammaglobulinemia and selective IgA deficiency. The conditions complicated with RA are not uncommon. They are osteoporosis, Sjogren's syndrome, amyloidosis and so on. There are some rare conditions or diseases which will be able to develop to RA. These peculiar cases include juvenile rheumatoid arthritis, adult onset Still's disease, polymyalgia rheumatica and palindromic rheumatism.     

新型移植诱导剂阿来佐单抗临床应用中的护理程序

将阿来佐单抗成功应用于尸体肾移植前免疫诱导21例、单纯胰岛细胞移植围手术期免疫诱导7例、尸体肾移植联合胰岛细胞和间充质干细胞移植前免疫诱导1例.通过严格、及时、正确的病房管理,肺部、会阴部、皮肤、饮食、心理等护理,以上病例术前用药过程顺利,未出现不良反应者11例占38%,高血压者18例占62%,寒战3例占10%,高热3例占10%,支气管痉挛1例占3%.经应对症处理后,29例患者全部病情平稳,完成用药计划且术后均未发生急件排斥反应,出院后随访最长时间为2年,最短时间为6个月,结果亦未有移植物排斥指征.但是,阿来佐单抗在移植前免疫诱导的长远疗效,还有待通过患者长期随访,以进一步观察阿来佐单抗的诱导治疗效果,并观察长期T淋巴细胞减少所致的相关不良作用.     

Some aspects of pathogenesis of ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the spine (spondylitis) and sacroiliac joints (sacroileitis) associated in many cases with inflammatory affection of the peripheral joints (arthritis), entesises (entesitis), eyes (uveitis), intestine (enteritis) and aortic root (aortitis). AS is considered now as a prototype of diseases from the group of seronegative spondyloarthritis. AS is a hereditary disease. Predisposition to AS (90%) is associated with genetic factors the key gene of which is HLA-B27. As pathogenesis of AS is not still verified, three hypotheses are considered basing on HLA-B27 biology. The role of environmental factors involved in AS development (tension in enteses and infection) are discussed.     

Targeting CVD risk in chronic connective tissue disease

Chronic inflammatory rheumatological conditions are associated with an increased burden of cardiovascular disease (CVD). In both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) most excess mortality is cardiovascular. Increased CVD risk is also associated with psoriatic arthritis, ankylosing spondylitis, antiphospholipid syndrome and systemic sclerosis. Several studies report that CVD mortality increases early in disease in RA, with increased risk of MI within one year and increased risk of hospital admission for CVD within seven years of diagnosis. A linear association has been demonstrated between subclinical carotid atherosclerosis and raised inflammatory markers. SLE is associated with 2-10 times the risk of a CVD event compared with the general population. CVD is now a leading cause of morbidity and mortality in SLE. Antiphospholipid antibodies are associated with accelerated atherosclerosis, as well as thromboses. Atherogenesis in the context of autoimmune disease results from a complex interplay between traditional risk factors, disease-specific factors and drug-related adverse effects. Chronic inflammation itself modifies the lipid profile.     

两种血清循环免疫复合物测定方法的比较

目的　对测定血清循环免疫复合物 ( circulating immune complexes,CIC)的两种方法 ( PEG沉淀法及 CIC-C1 q ELISA法 )进行评价 ,进一步探讨 CIC测定的临床意义。方法　采用 PEG沉淀法和 CIC-C1 q ELISA法检测肾脏损害、系统性红斑狼疮 ( SLE)、类风湿性关节炎 ( RA)等 86例患者的血清 CIC。结果　 86例患者中 PEG沉淀法检测阳性 1 7例 ( 1 9.77% ) ,CIC-C1 q ELISA法检测阳性 3 8例 ( 4 4.1 9% ) ,差异有显著性 ( P<0 .0 5 )。CIC-C1 q ELISA法检测 SLE、RA和肾脏损害患者的 CIC阳性率分别为 1 1 /1 5、5 /8和 2 0 /61 ( 3 2 .79% )。结论　与 PEG沉淀法相比 ,CIC-C1 q ELISA法较敏感 ,适宜于临床推广应用。CIC的阳性与 SLE、RA和肾脏损害有关。     

Plasmapheresis for patients with RA]

Effect of plasmapheresis for patients with rheumatoid arthritis. Plasmapheresis for rheumatoid arthritis (RA) was performed more than ten years, but efficacy of plasmapheresis was not done. In this paper, we discussed efficacy, indications and procedures. We have many procedures of plasmapheresis, 1) plasma exchange, 2) double filtration plasmapheresis, 3) cryofiltration plasmapheresis, 4) immunoadsorption plasmapheresis, 5) salt-amino acid coprecipitation plasmapheresis, 6) lymphocytapheresis, 7) lymphocyte-plasmapheresis, 8) photopheresis. Indications of plasmapheresis for RA are 1) malignant RA, 2) high activity of RA, 3) positive circulating immune complexes, 4) patients can't take steroid hormone or anti-inflammatory drugs. Efficacy of plasmapheresis for RA was not done, then, we must have controlled study about efficacy of plasmapheresis for RA.     

Current topics on cryofiltration technologies.

In the last 40 years, therapeutic plasmapheresis techniques have been improving considerably. These include cryofiltration technologies providing novel ways of removing large amounts of cryoproteins from plasma. The concept of cryofiltration involves exposure of plasma to below core (37 degrees C) and room temperatures (25 degrees C) without freezing. It was initially used to treat diseases such as cryoglobulinemia with systemic vasculitis, rheumatoid arthritis, systemic lupus erythematosus, and ABO-incompatible transplants. There are 2 basic types of cryofiltration. The first method removes cryoproteins, namely cryoglobulins that precipitate at 4 degrees C. Several filters have been used for this procedure like the AP06M (Asahi Medical, Tokyo, Japan) with a 0.2 microm pore size, a 0.65 m2 surface area, and a cellulose diacetate (CDA) membrane. It has been used in the United States and Japan for treatment of rheumatoid arthritis and cryoglobulinemia. A major disadvantage was frequent filter plugging, which was cumbersome and it is no longer used in the United States. The G3 cryofilter (Gelman Sciences, Ann Arbor, MI, U.S.A.) with a 3 microm pore size was tried in vitro but proved inadequate by design. Currently in our institution, the cryoglobulin filter (Pall Medical, Ann Arbor, MI, U.S.A.) is used with a 4.3 microm pore size, a 0.135 m2 surface area, and an acrylic co-polymer pleat membrane. We performed over 1,200 procedures in 40 patients in the last 8 years. The second type of cryofiltration removes cryogel, which is an agglutination complex of fibrinogen, fibronectin, fibrin split products, and cold insoluble proteins with a heparin core, at temperatures between 2 and 10 degrees C. The AP06M, the AC1740 (Asahi Medical) with a 0.02 microm pore size, a 1.70 m2 surface area, and a CDA membrane, and the Evaflux-4A (Kuraray Company, Osaka, Japan) with a 0.03 microm pore size, a 2 m2 surface area, and an ethylene vinyl alcohol membrane are used to remove cryogel to treat ABO-incompatible transplants as well as rheumatoid arthritis and other previously mentioned diseases. This article will discuss each cryofiltration treatment modality.