Immunoglobulin clases IgG, IgM, IgA and complement component C3 in dental periapical lesions of patients with rheumatoid disease.

To identify the immunoglobulin classes present in dental periapical lesions and to determine how, if at all, the distribution of immunoglobulin classes IgG. IgM and IgA differ in the dental periapical lesions of rheumatoid and control patients, paraffin-embedded and frozen tissues from the dental periapical lesions of 36 rheumatoid and 22 control patients were examined by the direct immunofluorescence technique. In addition, both rheumatoid and control tissues were examined for the presence of complement component C3, albumin and fibrinogen. Neither the greater frequency and abundancy with which IgG and to a lesser degree, IgA occurred in the dental periapical lesions of rheumatoid patients than in the corresponding lesions of control patients, nor the more frequent occurrence of complement component C3 in these same lesions, was statistically significant. No difference in the distribution of the various immunoglobulin classed could be discerned between the rheumatoid and control group. Albumin was distributed almost equally between the two patient groups. The greater abundance of fibrinogen among control patients was, however, statistically significant. These results do not provide evidence that an immunologic reaction takes place in the dental periapical lesions of patients with rheumatoid disease similar to that which characterizes rheumatoid inflammation. However, the presence of such a reaction cannot be excluded without more extensive investigation.     

Immunopathologic findings in idiopathic renal hematuria.

Eighty patients had idiopathic renal hematuria and normal renal function. Renal biopsy showed minimal changes or focal glomerulonephritis in two thirds of the patients. The remainder exhibited diffuse proliferative glomerulonephritis and included nine patients with segmental glomerular sclerosis. Electron microscopy disclosed alterations of the capillary loop in 23 biopsy specimens and electron-dense deposits in 11. Immunofluorescent microscopy identified glomerular-bound immunoglobulins, C3, or fibrinogen in 58% in a generalized distribution. IgG was the immunoglobulin seen most commonly. IgA and IgM were present in 14 and 13 biopsy specimens, respectively. These findings suggest that idiopathic renal hematuria is a clinical syndrome rather than a single disease with varying underlying renal findings. Both immunologic and nonimmunologic mechanisms may be involved, and the prognosis is favorable even in patients followed up for 11 years.     

Acute-phase proteins and serum immunoglobulins in ankylosing spondylitis.

The erythrocyte sedimentation rate (ESR) and the serum acute-phase proteins (APP), C-reactive protein (CRP), fibrinogen, 9th component of complement (C9), and alpha, antitrypsin were measured on 231 occasions in 80 patients with ankylosing spondylitis and compared with those in 30 controls. APP levels did not correlate with clinical assessment of disease activity. However, there were significant correlations between CRP, C9, and fibrinogen (p = less than 0.01), suggesting that these APP may be more reliable indicators of disease activity. The mean values of the APP in those patients with a peripheral arthritis were significantly higher than in those with pelvospondylitis alone for ESR (p less than 0.01), CRP (p less than 0.01), and fibrinogen (p less than 0.05). The only significant difference between those patients with an iritis and those with only pelvospondylitis was an elevated CRP in the iritis group (p less than 0.01). This suggests that a peripheral arthritis is the most important cause of an elevated ESR or APP in ankylosing spondylitis. Serum immunoglobulins were also measured and they showed a significant elevation of IgA in all 3 patients groups, there being no difference between each group. Serum IgG was raised only in those patients with an iritis or peripheral arthritis, the IgM levels being within the normal range for all patient groups.     

血浆同型半胱氨酸与系统性红斑狼疮关系的探讨

目的探讨系统性红斑狼疮(SLE)与血浆同型半胱氨酸(Hcy)间的关系,并分析影响SLE患者Hcy的代谢因素.方法 60例SLE患者和正常对照组45例,测定并分析血浆Hcy水平与叶酸、维生素B12、IgG、IgA、IgM、C3、C4、C反应蛋白(CRP)、血沉(ESR)各指标之间的关系.结果 (1)SLE组血浆Hcy、IgG、IgA、IgM、CRP、ESR水平均显著高于正常对照组(P<0.05);叶酸、维生素B12 、C3、C4均显著低于正常对照组(P<0.05).(2)SLE组患者Hcy与IgG、IgA、IgM、CRP呈正相关,与叶酸、维生素B12、C3、C4水平呈负相关(P<0.05),与ESR无相关性.(3)正常组血浆Hcy浓度与各指标无相关性.结论 Hcy水平升高与SLE密切相关,SLE患者普遍有高Hcy血症,血浆Hcy的检测对于SLE病人有临床应用价值.     

Autologous IgM, IgA, and complement binding to sickle erythrocytes in vivo. Evidence for the existence of dense sickle cell subsets

We have previously reported that sickle erythrocytes sedimenting at high specific density after gradient centrifugation exhibit increased IgG binding in vivo as compared with low-density paired samples. We have performed the present study to determine whether the opsonization of dense sickle cells in vivo could also involve autologous IgM, IgA, and complement. IgA, IgM, and complement binding in vivo to the surface of density-separated sickle erythrocytes was detected by flow cytometric analyses. IgM and complement C3 fragment binding was detected primarily on high-density sickle erythrocytes. With the exception outlined below, IgA binding was detected for all sickle cell fractions that sediment at densities > 1.085 g/mL. IgM, IgA, and complement C3 fragment binding was increased on high-density sickle erythrocytes as compared with low-density paired samples and exceeded that binding to normal erythrocytes by 30% +/- 10% (mean +/- range), 50% +/- 10%, and 41% +/- 5%, respectively. Two-color flow cytometry indicates that high-density sickle cell fractions contain at least two heterogeneous RBC subsets. One is an RBC subset that binds IgA in combination with IgM and C3, and the second subset is devoid of IgA yet binds IgM and C3. These findings indicate that high-density sickle cells exhibit a greater heterogeneity than has been reported in previous studies, which is based on autologous Ig binding in vivo; and suggest that RBC components of this most severely dehydrated sickle cell subpopulation could have heterogeneous origin and pathophysiologic significance. Although the functional role of IgA binding to human RBCs is unclear, our findings that IgM and complement bind to the same high- density sickle cell fractions suggest that both the IgM and the sickle erythrocyte-bound IgG determined in previous studies could mediate the deposition of complement on dense sickle cells in vivo. These findings support the hypotheses that irreversibly sickled cell-enriched high- density sickle RBC subpopulations could be removed from the circulation by erythrocyte phagocytosis that is enhanced by the presence of complement.     

Sickle discocytes form more rouleaux in vitro than normal erythrocytes

Rouleaux formation of washed erythrocytes was studied in 32 normal (HbAA) individuals and 30 sickle cell anaemia (HbSS) patients. Washed red cells were suspended in their plasma and rouleaux formation visualized with the aid of an inverted microscope connected to a video camera-monitor unit. Aggregation rate was studied by visual particle counting. Washed sickle discocytes showed rouleaux formation three times as high as normal cells. Red cells were also suspended in buffered Ringer solution containing dextran (a rouleaux inducer). Again, washed erythrocytes from sicklers were about 3 times more aggregable than normal cells at all pH values studied. Increased acidity appeared to aggravate rouleaux formation in both Hb genotypes. We also found plasma fibrinogen concentration in sicklers to be about twice as high as that of normals. High rouleaux formation in sicklers could be attributed not only to fibrinogen and other plasma factors but also to cellular factors.     

Immunoglobulins on the surface of monosodium urate crystals: an immunoelectron microscopic study

The ability of monosodium urate (MSU) crystals to bind immunoglobulins from human serum was investigated by immunoelectron microscopy. Synthetic MSU crystals were incubated with serum and then processed with an indirect immunoperoxidase technique which used primary antibodies directed against human IgG, IgA or IgM, respectively specific for Fc fragments, alpha chains, and mu chains. Results were analyzed by transmission electron microscopy on intact crystals dried on formvar coated grids, and in thin sections. Both techniques demonstrated the binding of IgG, IgA and IgM to MSU crystals and the availability of the Fc fragment of the crystal bound IgG for immunologic reactions.     

Inflammation-sensitive proteins and erythrocyte aggregation in atherothrombosis

OBJECTIVE: To find the relative contribution of various inflammation-sensitive proteins including fibrinogen, immunoglobulins (IgG, IgM and IgA), ceruloplasmin and high sensitivity C-reactive protein (hs-CRP) to the induction and/or maintenance of enhanced erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors. METHODS: The degree of erythrocyte adhesiveness/aggregation was determined by a simple slide test and image analysis. In addition, we measured various inflammation-sensitive protein levels including fibrinogen, ceruloplasmin, immunoglobulins and hs-CRP in a group of 234 individuals with atherothrombotic risk factors and healthy ones. Pearson partial correlations and multiple linear regression analysis were performed. RESULTS: Fibrinogen was found to be the major protein contributing to the enhanced erythrocyte adhesiveness/aggregation, explaining 30% of the model. Fibrinogen and IgG together explained 32.4% of the model. Other inflammation-sensitive proteins did not reach statistical significance and were excluded from the model. CONCLUSIONS: Among inflammation-sensitive proteins measured in our cohort, fibrinogen is the dominant contributor to erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors and healthy ones. These findings may pave the way for the development of therapeutic strategies directed at the attenuation of erythrocyte aggregability in individuals with atherothrombosis.     

Prognostic laboratory markers of joint damage in rheumatoid arthritis

OBJECTIVE: To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in hands and feet in rheumatoid arthritis. METHODS: 183 patients with early rheumatoid arthritis included in a prospective study were examined. Radiographic changes in hands and feet at 5 and 10 years after inclusion were evaluated (Larsen). The markers analysed were: erythrocyte sedimentation rate (ESR); HLA-DRB alleles typed by restriction fragment length polymorphism; and C reactive protein, cartilage oligomeric matrix protein (COMP), rheumatoid factor (RF) (IgG, IgA, and IgM subtypes), antibodies against cyclic citrullinated peptide (anti-CCP), and antibodies against interleukin 1alpha (anti-IL1alpha), analysed by immunoassays. Multiple linear regression with backward elimination was used to determine the prognostic value of the variables. RESULTS: 117/176 patients were positive for IgG RF, 138/176 for IgA RF, 139/176 for IgM RF, 140/176 for anti-CCP, and 40/182 for anti-IL1alpha. After five years, ESR, the presence of IgA RF, serum COMP, and the presence of anti-CCP were significantly associated with more severe joint damage, and the presence of anti-IL1alpha with less severe joint damage. Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years. A stronger prediction was obtained by combining the prognostic factors. CONCLUSIONS: Early determination of anti-CCP, IgA RF, anti-IL-1alpha, ESR, C reactive protein, and COMP predicted the development of joint damage in hands and feet in this cohort. A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis.     

Some characteristics of aggregates of IgG and plasma proteins in heat-treated factor VIII concentrates

Summary Eight batches of commercial heattreated and one untreated factor VIII concentrate from 6 producers were analyzed for their content of IgG, IgG subclasses, IgG aggregates and the presence of other plasma proteins combined with the IgG as well as for anticomplement activity. Methods used were thin-layer gel filtration, immuno-gel filtration, spot immuno-precipitate assay in a double antibody version and an agarose plate haemolysis inhibition assay of complement fixation. The IgG content varied from 0.1–6.90 g/l. In all preparations IgG existed as monomers and aggregates. Associated with the IgG were also found, at significantly increased amounts compared to normal serum and intravenous immunoglobulin, one to four of the following plasma proteins; fibronectin, fibrinogen, von Willebrand factor antigen, Clq, albumin and IgA. Three batches from two producers had high anticomplementary activity, presumably caused by the IgG aggregates. Two of these deviated strikingly from normal human serum pools in percent distribution of IgG subclasses. It is hypothesized that these aggregates can induce side effects or cause immunological aberrations.     

Secretory IgA: immune defence pattern in ankylosing spondylitis and klebsiella.

Saliva secretory IgA (sIgA), secretory component (SC); serum immunoglobulins (IgG, IgA, IgM), complement (C3, C4), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were performed in 32 patients with ankylosing spondylitis and 29 normal controls. They were investigated for carriage in the faeces of Klebsiella spp. on 3 occasions over the previous months. Throat swabs and urine were cultured at the same time as immunological estimations were done. 24-hour urine sIgA specimens were studied in 13 patients and 12 normal controls. Significantly raised mean values of saliva sIgA and serum IgG, IgA, C3, and C4 were found in patients with raised values of serum ESR and CRP levels when correlated with controls. Raised values of sIgA in saliva, which is an important factor of the local immune defence mechanism of mucosal surfaces, suggests the presence of an antigenic stimulus from the gastrointestinal system in ankylosing spondylitis during activity of disease.     

Evans' Syndrome in IgA Deficiency Episodic Autoimmune Haemolytic Anaemia and Thrombocytopenia during a 10 Years Observation Period

A 26-year-old male with a 10-year history of complete selective IgA deficiency and recurrent autoimmune anaemia and thrombocytopenia (Evans syndrome) is presented. Both serum IgA and saliva secretory IgA were below the detection limit (< 0.05 mg/1). No other features of autoimmunity were seen. The patient had a normal % of peripheral blood lymphocytes with surface IgM and IgG cells and normal in vitro lymphocyte transformation after stimulation with mitogens and antigens. The pleomorphic and randomly appearing immunologic features of selective IgA deficiency are emphasized by the present case.     

Soluble proteins in the human atherosclerotic plaque. With spectral reference to immunoglobulins, C3-complement component, alpha 1-antitrypsin and alpha 2-macroglobulin.

A number of soluble proteins contained in human aortic intimal tissue was extracted into buffered saline (pH 7.4) and identified and quantitated by immunoelectrophoresis and immunodiffusion. The proteins included IgA, IgG, IgM, B1C (C3), alpha 1-antitrypsin, alpha 2-macroglobulin, fibrinogen, albumin, LDL, HDL, alpha 1-acid glycoprotein, beta 2-glycoprotein, transferrin and ceruloplasmin. The concentration of soluble proteins was significantly higher in the atherosclerotic intima than in the normal intima. The diseased intima also contained a small amount of tissue-bound IgG, IgA and B1C which was extractable with citrate buffer at pH 3.2. The vascular band IgG, and B1C were shown by enzymatic and immunohistochemical studies to be closely associated with the collagenous tissue of the plaque. The Ig contained in the atherosclerotic plaque may be derived in part from the biosynthesis of Ig by the artery, since the incorporation of 14C-labeled leucine into IgG by the atheromatous plaque was demonstrable by radioimmunoelectrophoresis. In contrast to the diseased artery, the normal artery did not synthesize IgG and did not contain vascular bound IgG or complement. However, the normal artery was capable of fixing IgG and B1C eluted from the diseased artery. The present studies suggested that the IgG contained and synthesized by the plaque might represent an immune response to an endogenous or exogenous antigen closely associated with plaque collagen. IgG and B1C either alone or in the form of an immune complex also may play an important role in phagocytosis in the plaque and thereby influence the course of atherosclerosis. The proteolytic inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, found in relatively high concentrations in the plaque, could enhance fibrosis of the lesion because of thier known inhibitory effects on collagenase and elastase.     

Platelet IgG, IgA, IgM, and albumin: correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia

IgG, IgA, IgM, and albumin are primarily known as plasma proteins. Their presence in platelets is poorly understood. The total platelet content of IgG, IgA, and albumin, measured in solubilized platelets by an enzyme-linked immunosorbent-assay (ELISA) technique, was greater than 90% secreted after stimulation by thrombin, consistent with an alpha-granule location. The platelet concentrations of these proteins correlated with their plasma concentrations in normal subjects and over a wide range of abnormalities in patients with IgG or IgA myeloma or liver cirrhosis. IgM was not detectable in normal platelets but was measurable and related to the plasma IgM concentration in patients with macroglobulinemia. In patients with idiopathic thrombocytopenic purpura (ITP), the platelet concentrations of IgG, IgA, and albumin were all twofold to threefold higher than normal despite normal plasma concentrations. Platelet surface IgG, measured by 125I-monoclonal antibody binding, constituted less than 1% of the total platelet IgG, and it appeared to be a pool distinct from the alpha-granule IgG since its concentration in normal subjects and patients did not correlate with either plasma or total platelet IgG concentrations. These observations are consistent with hypotheses that megakaryocytes incorporate plasma proteins into developing alpha-granules by pinocytosis and that the increased ratio of platelet to plasma of IgG, IgA, and albumin in ITP may reflect a younger average age of these platelets.     

Quantitation of cells secreting rheumatoid factor of igg,iga, and igm class after elution from rheumatoid synovial tissue

In an indirect hemolytic plaque assay that used sheep erythrocytes coated with normal rabbit IgG or reduced/alkylated IgG anti–sheep erythrocytes, mononuclear cells eluted from rheumatoid synovial tissue of 7 of 11 patients with seropositive rheumatoid arthritis contained cells that secreted rheumatoid factor of IgG, IgA, and IgM classes. The number of rheumatoid factor–secreting cells varied from <1% to 53% of the total number of eluted immunoglobulin-secreting cells. In contrast, immunoglobulin-secreting cells and rheumatoid factor–secreting cells were scanty in blood compared with synovial tissue mononuclear cells.     

The influence of pregnancy on blood parameters in patients with rheumatic disease

To evaluate the mutual effect of pregnancy and rheumatic disease, 17 laboratory parameters have been monitored in 10 patients with rheumatoid arthritis (RA) and 13 patients with ankylosing spondylitis (AS), studied prospectively during and after gestation. Thirty-one healthy pregnant women served as controls. In the two patient groups, laboratory measurements during gestation, including several acute phase proteins, paralleled those found in healthy controls, indicating that rheumatic disease has no adverse effect on pregnancy. When the non-pregnant period was evaluated, elevated levels of IgG and IgM in RA and elevated ESR and IgA appeared to be predictive indices of the gestational remissions of RA and AS. Thus, a specific immunologic reactivity may be the main condition for remission during pregnancy.     

High-dose intravenous methylprednisolone in rheumatoid arthritis.

Fourteen patients with severe rheumatoid arthritis (RA) were given 27 courses of methylprednisolone intravenously, each of 3 infusions of 1 g on alternate days. After 7 days there was marked improvement in clinical state and most laboratory tests; levels of ESR and 4 serum acute-phase proteins, C3, C, IgG, and IgA, fell significantly. Serum IgM and rheumatoid factor titre were unchanged. 125I C1q binding fell in all instances where it was initially raised. Clinical remission lasted a mean of 10 weeks. Serum C-reactive protein (CRP) fell to less than 30 mg/l after all courses except one within 7 days and rose above this figure after a mean of 7 weeks. The ESR fell below 30 mm/h within seven days in 17 courses and remained below this value for a mean of 7 weeks. Three patients had clinical remissions, with serum CRP less than 30 mg/l and ESR less than 30 mm/h, lasting more than 42 weeks.     

硬膜外注药治疗腰椎间盘突出症对患者体液免疫因子的影响

为观察三膜外注药对腰椎间盘突出症患者体液免疫因子的影响，将61例腰椎间盘突出症患者按椎间盘突出程度分为两组，A组髓核突出≥0．5c m，B组＜0．5cm，采用单向免疫扩散法检测硬膜外注药前后两组血清IgG,IgA,IgM和C3等体液免疫指标的变化，并与31例正常人（对照组）进行比较，结果显示：A组治疗前血清IgG,IgM和B组和对照组增高（P＜0．05），B组与对照组比较无明显差异（P＞0．05），治疗后A组各项指标达到正常范围，表明腰椎间盘突出症患者存在免疫反应性炎症及体液免疫异常，且其严重程度与椎间盘突出程度呈正相关，硬膜外注药可调节患者的免疫功能紊乱状态，消除受胃神经根的免疫反应性炎症     

恶性血液病患者血液感染时免疫球蛋白水平

日的对恶性血液病患者血液感染时的免疫球蛋白水平与非感染患者进行对照研究,探讨影响恶性血液病患者血液感染的体液免疫因素。方法将36例恶性血液病患者分为两组,合并血液感染患者和非感染患者各18例,散射比浊法检测两组血清IgG、IgA、lgM、C3、C4;法国梅里埃公司VITEK-60System全自动细菌分析仪鉴定菌种。结果两组患者血清IgG、IgA、IgM、C3,C4水平统计学上无显著性差异,感染组、非感染组与正常对照组相比除C4外也无显著性差异。结论血清免疫球蛋白的含量多少不是导致恶性血液病患者血液感染的重要因素,而免疫球蛋白的质量低下或者抗体活性降低可能是导致血液感染的主要因素之一。     

Ceruloplasmin and immunoglobulins under controlled D-penicillamine therapy in rheumatoid arthritis]

In a controlled therapeutic trial 17 patients with active rheumatoid arthritis (stage II and III) were divided in two randomized groups. One group of 9 patients was treated with 900 mg of D(-)penicillamine (Trolovol) plus 1500 mg of salicylate per day, the other group of 8 patients with 10 mg of prednisolone plus 1500 mg of salicylate daily. Before and after 1, 2, 3, 4 and 6 months of treatment IgA, IgG, IgM and caeruloplasmin were estimated with immunodiffusion technique. In both groups the IgA and IgG levels remained unchanged; unter D-penicillamine, on the contrary, a statistically significant and continuous fall of IgM and caeruloplasmin was observed; prednisolone treatment induced only a temporary fall of caeruloplasmin. In the DPA treated patients, a significant correlation of IgM with caeruloplasmin and of caeruloplasmin with ESR was found. In both groups there was no correlation between joint count and caeruloplasmin, joint count and IgM, caeruloplasmin and copper, copper and ESR; in the prednisolone group no correlation between caeruloplasmin, ESR and IgM was observed. The correlations suggest that the remarkable fall of IgM and caeruloplasmin under D(-)penicillamine treatment is caused at least partially by direct interference of DPA with these plasma proteins.