IgM Globulin Research Articles

Potential role of plasmapheresis in severe cytomegalovirus infection with ongoing immunemediated hemolysis and low complement level

Symptomatic cytomegalovirus (CMV) infections are rare in patients with no previous history of immunosuppressive therapy or condition. A 33-year-old woman with type-2 diabetes, endstage renal disease (ESRD) and unexplained lower extremity weakness was admitted with failure to thrive, ongoing hemolysis, low haptoglobin and C3 levels and suppressed IgM and IgG globulin fractions. Multiple cultures and serologic workup for autoimmune disorders remained negative. CMV viral titer by serum polymerase chain reaction (PCR) revealed massive elevation at 9.2 million copies/mL. Initial CMV IgG titer was positive, IgM titer remained consistently negative and CMV was recovered from cerebrospinal fluid, as well. She received treatment with I.V. ganciclovir, CMV immune globulin (CytoGam) and three sessions of plasmapheresis (PLEX). The extreme viremia without neutropenia, lack of IgM antibody reconversion and CMV-mediated hemolysis with a low complement level were all very unusual features. Timely initiation of PLEX may have contributed to recovery

Clinical analysis of 85 cases of dermatomyositis combined with interstitial lung disease

Objective To analyze the clinical features of patients with dermatomyositis (DM)/polymyositis (PM) associated with interstitial lung disease (ILD).Methods Clinical data were collected on 432 inpatients with DM/PM from September 2004 to June 2012 in the No.1 Hospital of China Medical University.Of these patients,85 with and 79 without complicated ILD were eligible for this study.All statistical analyses were carried out using SPSS 17.0 software.Chi-square test was performed for count data analysis,and t test for measurement data analysis.Results The incidence rate of fever was significantly higher (55.29％ (47/85) vs.22.78％ (18/79),P ＜ 0.05),but that of dysphagia was significantly lower (10.59％ (9/85) vs.24.05％ (19/79),P ＜ 0.05),in patients with complicated ILD than in those without.Moreover,the patients with complicated ILD showed significantly decreased serum levels of creatine kinase (CK) and l-lactate dehydrogenase (LDH) but increased levels of IgA,IgM,IgG and gamma globulin compared with those without complicated ILD (all P ＜ 0.05).Conclusions Compared with DM/PM patients without complicated ILD,those with complicated ILD are more likely to have fever with slightly elevated levels of CK,LDH and evidently elevated levels of IgA,IgM,IgG and gamma globulin in serum.Male patients with DM/PM seem to be more prone to ILD than female patients. Key words: Dermatomyositis; Polymyositis; Lung diseases, interstitial; Retrospective studies

Protein profiling of Guillain–Barrè syndrome cerebrospinal fluid by two-dimensional electrophoresis and mass spectrometry

Protein profiling of cerebrospinal fluid in Guillain–Barrè syndrome (GBS), an acute and immune-mediated disease affecting the peripheral nervous system, was performed by two-dimensional electrophoresis. Significant modulated spots in GBS patients vs. control groups (a group of multiple sclerosis patients and one of healthy donors) underwent MALDI-TOF/TOF investigation. Inflammation-related proteins, such as vitamin D-binding protein, beta-2 glycoprotein I (ApoH), and a complement component C3 isoform were up-regulated in GBS, whereas transthyretin (the monomer and the dimer forms), apolipoprotein E, albumin and five of its fragments were down-regulated. Then, we used an isoelectric-focusing-dinitrophenylhydrazine-based technique to analyse the extent of carbonylation and, as a result, of oxidative damage of GBS CSF proteome. We observed a major sensitivity to carbonylation for albumin and alpha-glycoprotein in inflammation and a selective increase of reactivity for a glycosylated Fab from an IgM globulin in GBS CSF. Our results add new proteins to candidate CSF features of GBS, and suggest that oxidative stress could contribute to the immunopathological mechanisms in this syndrome.

Serum immunoglobulins in psoriasis before and after ultra violet light therapy.

SUMMARY.— A significant increase of the mean IgA globulin value was noted in 105 patients with ordinary psoriasis whereas the mean IgG and IgM globulin levels remained normal. Thirty-two of these patients received u.v. light therapy which resulted in resolution of the skin lesions. At this stage the IgA levels fell to the normal range. The possibility of the skin eruption influencing the IgA serum levels is discussed.

正常ヒト血清の莢膜保有<I>Staphylococcus hyicus</I> ST67P株に対する感染防御活性について

Five tenths ml of passive protective antibodies in 100 samples of normal human sera against challenge with an encapsulated strain ST67P of Staphylococcus hyicus in mice were examined. Thirty three of them passively protected in mice against infection with strain ST67P of S. hyicus. The activities were sensitive to 2-mercaptoethanol and were absorbed out either with rabbit anti-human IgG, IgM or IgA serum. Also, the serum activities were absorbed out with cell surface polysaccharide extracted from the cell surface substance of the strain. When passive protective human serum was absorbed out with cell surface polysaccharide, reduction of IgG, IgA and IgM contents were 14.48, 19.49 and 33.3 percent, respectively, while 2.17, 4, 55 and zero in non protective human serum. These results indicate that the protective activities against strain ST67P were specifically related to IgM globulin against the above cell surface polysaccharide.

Retrospective diagnosis of Q fever in a country abattoir by the use of specific IgM globulin estimations

Twenty-two cases of pyrexial illness which occurred amongst workers in a country abattoir were investigated retrospectively for Q fever, brucellosis, and leptospirosis. In 18, the illness was shown to be Q fever. No diagnoses were established for the other four. The demonstration of circulating Q-fever-specific IgM globulin was instrumental in establishing the diagnosis in many of the cases.

IgM globulin response in Q fever (Coxiella Burneti) infections

The IgM globulin response has been measured following the onset of primary Q fever infections. A complement fixation test method was used to measure the IgM after separation by ultracentrifugation in a sucrose density gradient. Specific IgM was demonstrable between 2 and 10 wk after onset of symptoms. The test can be used to confirm a recent infection when only a 'convalescent' blood specimen has been collected and will be useful in the assessment of workers' compensation claims.

Serum immunoglobulin levels in patients with neuroblastoma and their prognosis

Serum IgG, IgA, IgM and β1A globulin levels of 24 patients with neuroblastoma were measured for the purpose of determining whether or not humoral immune competence of these patients is related to their prognosis. As control groups, 39 normal children and 21 patients with other melignant neoplasia such as leukemia and malignant lymphoma were measured for these globulin levels. On admission, the serum IgG level was high in 7/16 (43.8%) of the neuroblastoma patients, in 0/39 (0%) of the normal children and in 2/21 (9.5%) of the other malignancies (>M+2 SD). β1A globulin level was high in 10/16 (62.5%), 0/39 (0%) and 8/21 (38.1%) of the cases, respectively. Serum IgG and β1A globulin levels were observed to be higher in patients with neuroblastoma than in normal children and patients with other malignancies. Six of these 16 neuroblastoma patients are still alive: 3 with long survival with metastatic tumor and 3 with long survival without tumor. Four of these 6 patients, the first 3 cases and one of the latter cases, had very high IgG levels on admission (>M+3 SD). There were no significant differences between neuroblastoma, other malignancy and normal children in serum IgA and IgM levels. During serial measurement of these globulins in the 14 dying cases, serum IgG level decreased abruptly 2–4 mo after the initial treatment whereas the initial high levels continued in all of the living cases. β1A globulin registered high levels on admission in both dying and living patients and gradually decreased during treatment. All 4 cases with recovery showed normal ranges (M+1 SD). As a result, patients who showed a higher level of IgG at admission and did not have decreased IgG and IgM levels during treatment seemed to be long survival cases. We think that these data suggest that the humoral immune competence of the patients with neuroblastoma may be related to their prognosis. Serum IgG, IgA, IgM and β1A globulin levels of 24 patients with neuroblastoma were measured for the purpose of determining whether or not humoral immune competence of these patients is related to their prognosis. As control groups, 39 normal children and 21 patients with other melignant neoplasia such as leukemia and malignant lymphoma were measured for these globulin levels. On admission, the serum IgG level was high in 7/16 (43.8%) of the neuroblastoma patients, in 0/39 (0%) of the normal children and in 2/21 (9.5%) of the other malignancies (>M+2 SD). β1A globulin level was high in 10/16 (62.5%), 0/39 (0%) and 8/21 (38.1%) of the cases, respectively. Serum IgG and β1A globulin levels were observed to be higher in patients with neuroblastoma than in normal children and patients with other malignancies. Six of these 16 neuroblastoma patients are still alive: 3 with long survival with metastatic tumor and 3 with long survival without tumor. Four of these 6 patients, the first 3 cases and one of the latter cases, had very high IgG levels on admission (>M+3 SD). There were no significant differences between neuroblastoma, other malignancy and normal children in serum IgA and IgM levels. During serial measurement of these globulins in the 14 dying cases, serum IgG level decreased abruptly 2–4 mo after the initial treatment whereas the initial high levels continued in all of the living cases. β1A globulin registered high levels on admission in both dying and living patients and gradually decreased during treatment. All 4 cases with recovery showed normal ranges (M+1 SD). As a result, patients who showed a higher level of IgG at admission and did not have decreased IgG and IgM levels during treatment seemed to be long survival cases. We think that these data suggest that the humoral immune competence of the patients with neuroblastoma may be related to their prognosis.

Suppression of naturally occurring anti-tissue antibodies during growth and after removal of tumours.

The sera of normal rats were found to be active in the complement fixation test against isogeneic tumour homogenates. This activity was shown to be heat labile and to sediment with IgM globulins on zone ultracentrifugation in sucrose density gradients. Sera from rats bearing progressively growing tumours and sera from rats, which had such tumours excised, were found to be less active than normal rat sera in the complement fixation test against isogeneic tumour and liver homogenates. It was considered that this suppression of naturally occurring anti-tissue antibodies may be a specific process related to the host immune response to the tumour.

Auto-Anti-M antibody: a case following renal transplantation

An autoantibody of Anti-M specificity developed following haemodialysis and renal transplantation in a 25-yr-old man with rapidly progressive glomerulonephritis. Only 4 cases of Anti-M occurring as an autoantibody have been previously reported. The antibody was readily absorbed by and eluted from the patient's own red cells and was shown to be IgM globulin reacting optimally at 4°C. The patient's red cells appeared to have a normal M antigen. The antibody displayed similar characteristics to the more commonly found Anti-M alloantibody. There was no evidence of immune haemolysis. The antibody did not demonstrate features similar to the Anti-N like antibodies which have been described in patients undergoing chronic haemodialysis programmes. The significance of the renal transplant in relation to the formation of the antibody remains obscure.

Erythema Multiforme: Immune Complex Vasculitis of the Superficial Cutaneous Microvasculature

The specificity and incidence of deposits of immunoglobulin and complement in the walls of vessels in the superficial cutaneous microvasculature were evaluated in a prospective study of consecutive skin biopsy specimens submitted for evaluation by direct immunofluorescence. Of 597 specimens, 32 showed granular deposits of C3, either alone or associated with immunoglobulin in the vessels of the papillary dermis. In most cases, the immunoglobulin was identified as IgM. Rheumatoid arthritis was identified as the diagnosis in 19% of patients who were biopsied, while syndromes of vasculitis, connective tissue diseases and erythema multiforme were the diagnoses in 28%, 28% and 16% of the biopsies respectively. The immunofluorescent findings and inciting cause of 17 erythema multiforme lesions are presented. All biopsies from early lesions showed deposits of C3 alone, or with IgM globulin, in the microvasculature of the papillary dermis. Herpesvirus hominis (HSV) was the predisposing cause in 8 patients, and 9 patients had erythema multiforme of uncertain etiology. HSV antibody was predominantly IgG in 6 subjects as it was in 5 controls with recurrent HSV who did not experience erythema multiforme. This study suggests that deposits of immunoglobulin and complement in the superficial cutaneous microvasculature can be found in a wide spectrum of vasculitis syndromes, and that erythema multiforme is mediated by the deposition of immune reactants in these vessels.

Most IgM-producing cells in the mouse secrete auto-antibodies (rheumatoid factor)

IN the mouse the injection of bacterial lipopolysaccharide (LPS) results in the appearance of very large numbers of IgM globulin-secreting cells1. Furthermore, it has been shown that LPS induces B lymphocytes, both in vivo2,3 and in vitro4–6 to secrete IgM antibodies to a wide range of seemingly unrelated antigens. It was reported recently that about 8% of all IgM globulin-secreting cells arising as a consequence of LPS injection into CBA mice secrete an antibody-like molecule with specificity for a heterospecific (bovine) IgG (BIG) molecule1. It was suggested that such IgM molecules were reminiscent of a rheumatoid factor, although at that time plaque-forming cells (PFC) had not been demonstrated using mouse IgG (MIG) as the target antigen. I have now been able to demonstrate the presence of auto-(anti-MIG)-antibody-forming cells. About half (35–75%) of all IgM-secreting cells appearing after both mitogen and immunogen injection into mice produce IgM globulin which is not specific for the inducing immunogen, but which does have specificity for self-IgG. The description by Steel and Cunningham7 of a large proportion of IgM-PFC having specificity for normally hidden (syngeneic) erythrocyte antigens, supports a view that a majority of both mitogen and immunogen stimulated IgM-PFC are producing auto-antibodies. Although a mouse rheumatoid-like IgM with binding activity against antigen-bound (syngeneic) IgG was described previously8, until now attempts to develop a haemolytic plaque assay for autologous mouse M-anti-G have failed. After unsuccessful attempts involving various forms of mouse IgG, partially denatured mouse IgG and also a procedure used successfully in the rabbit9, a successful method has been developed. An account of some of the results from experiments using this methodology is presented here.

IgM Participation in Tumor Rejection by Immunized MICE

IgG and IgM participation in tumor rejection was studied in DBA/2 mice immunized against L1210 leukemia and in Swiss mice immunized against Ehrlich adenocarcinoma. In both the systems, IgM globulins seem to be implicated and are present on the cell surface of macrophages, lymphocytes and cancer cells, while IgG globulins are present only on some lymphocytes. IgM are also present in the peritoneal washing fluids (obtained 24 h of the control group. In the former group, protein content is about three times higher than that in the control group, while the relative amount of heavy proteins (18 S) and light proteins (7 S) is quite similar. These observations are discussed, as is the possibility that some complement components as C3 may participate in the reaction.

Proteins retained with hyaluronic acid during ultrafiltration of synovial fluid.

The identity of the proteins associated with hyaluronic acid after ultrafiltration of bovine synovial fluid was examined. With discontinuous filtration, alpha2 macro- and IgM globulins were retained in hyaluronic complex both from synovial fluid and from a similar mixture of hyaluronic acid and serum. With continuous filtration and stirring to prevent formation of gels, protein was retained with hyaluronic acid in similar proportions. This protein showed immunologic identity with serum albumin, but differed in amino acid composition. After comparison with results of gel filtration, it was concluded that the identity of the retained proteins can be determined by the concentration of hyaluronic acid without variation in other ionic conditions.

Induction of an IgM anti-(bovine)-IgG response in mice by bacterial lipopolysaccharide.

BACTERIAL endotoxin stimulates the appearance in mice of a large number of plaque forming cells (PFC) secreting an IgM globulin with specificity for bovine IgG (bovine gamma globulin; BGG). Reversed plaquing (antibody on the target erythrocyte) has enabled us to enumerate the total number of IgM secreting cells and show that the anti-BGG PFC comprise at least 10% of the total. Plaque inhibition with free antigen shows that anti-BGG PFC stimulated by LPS, as distinct from those specifically stimulated, secrete a product with low avidity. The evidence reported both here and in a previous study1, leads us to suggest that substances such as LPS stimulate the production of an M-anti-G response. The rheumatoid-factor-like molecule which is produced may possibly serve to amplify complement fixation by high avidity/specificity IgG antibodies.

Quantitative determination of immunoglobulins, lysozyme, and certain electrolytes in breast milk during the entire period of lactation, during a 24-hour period, and in milk from the individual mammary gland.

During a period commencing at birth and lasting for up to 27 months 193 milk samples have been collected from 29 mothers. The IgA globulin content was high immediately after birth, averaging 2.7 arb.U, decreasing to 0.3 arb.U within the first 2 to 3 weeks after birth, then remaining almost constant for the rest of the lactational period. In the case of IgG globulin, similar results were obtained, but the quantity was much smaller. IgM globulin was demonstrated in small quantities during the first 3 weeks of lactation. The lysozyme content varied considerably during the whole lactational period. Individual variations were found for all the immunoglobulins, while the concentration in the individual woman varied only slightly from day to day following in other respects the pattern described above. In 19 mothers IgA, IgG, IgM, lysozyme and electrolyte content were determined in serum and in milk from the right and the left breast on the same day. No difference in content was found between milk from the left and the right mammary gland. A positive correlation was found between the concentrations of IgA and sodium chloride in milk, between those of IgG in milk and serum, and between those of lysozyme in milk and serum. No variations were registered during the individual breast feeding, nor for the 24-hour period as a whole.

Studies on a Circulating Anticoagulant in Systemic Lupus Erythematosus: Evidence for Inhibition of the Function of Activated Plasma Thromboplastin Antecedent (Factor XIa)

Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive

Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa)

Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive.

Evaluation of Human Sera for Antibodies Against Sperm by Immunofluorescence

Newborn cord sera and sera from pregnant women and from couples with unexplained infertility were observed by indirect immunofluorescence for reactions against human sperm. The sera from the infertile couples had been tested for macro-agglutination and complement-dependent immobilizing antibodies as well. Nonspecific fluorescence was noted only on the quatorial segment. Acrosomes and tail end-pieces were strongly immunofluorescent (positive at a serum dilution of 1:16) with 60 to 70% and 30 to 50%, respectively, of the sera from each main group, with the exception of the nonreactive cord blood. End-piece fluorescence was primarily due to the IgM globulin fraction. It is suggested that cord serum anti-sperm antibodies, directed mainly against the tail main piece, are due to IgG passively acquired from the mother. There was no apparent difference in immunofluorescence between infertile patients and control groups (except for the acrosome and end-piece, with cord sera). However, when the sera from infertile patients were subdivided into groups containing only agglutinating antibody, only immobilizing antibody, and both types of antibody, a higher percentage of the sera from the group having only agglutinating antibody reacted with all sperm areas. This reaction seemed more uniform over the sperm and included the usually negative posnuclear cap and midpiece. The other subgroups showed no obvious trends.

Immunological studies of the anticryptococcal factor of normal human serum.

Preliminary studies have shown a very high inhibitory activity in the alpha2 and gamma zone of human serum towards the growth of Cryptococcus neoformans. These findings are now corroborated by single radial immunodiffusion tests, which showed the some loss of IgA and IgM globulins and of the other three globulin fractions (ceruloplasmin, alpha2 macroglobulin and alpha2 HS glycoprotein) which migrate in the alpha2 zone. The data was obtained by single radial immunodiffusion tests. The losses were not statistically significant however. No change in the immunoglobulin content of the sera kept for 6 days in contact with a heat-killed suspension of C. neoformans was noted. These findings suggest, that the inhibitory activity of the normal human serum on the in-vitro growth of C. neoformans is due to the above mentioned globulin fractions and not to a single specific factor.