Positive Complement Fixation Reactions Research Articles

Multiple sclerosis: search for a serologic inhibitor.

Complement-fixing (CF) antibrain antibodies are frequently found in serum and CSF in multiple sclerosis (MS). A negative result in the test for these antibodies might depend not only on a lack of antibodies, but also on serologic inhibiting factors. To test this possibility, serum and concentrated CSF samples without demonstrable CF antibrain antibodies were allowed to interact with two standardized positive complement fixation reactions; one for antibrain antibodies and the other a Wasserman reaction. No evidence of inhibiting activity was found in 11 CSF and 15 serum samples from 20 MS patients. On the other hand, inhibiting activity was seen in serum from four of 12 patients with neoplasms and from three of 11 patients with rheumatoid arthritis.

A study of reproduction, disease and physiological blood and serum values in Idaho elk.

A study was conducted on elk (Cervus canadensis nelsoni) in the Selway-Bitterroot Wilderness and adjoining primitive area of the Clearwater drainage of Idaho over a 3 year period, 1969-1972. Midwinter examination of cows in this herd indicated the pregnancy rate was high, but game counts showed only 15 to 20 calves per 100 cows indicating that the losses occurred around or after calving. A serologic survey did not indicate the presence of antibodies to the agents of brucellosis, leptospirosis, vibriosis, bluetongue, infectious bovine rhinotracheitis or bovine virus diarrhea. Positive complement fixation reactions for anaplasmosis were present in nearly 50% of the animals tested; however, many of the serums were anticomplementary. Blood chemistry determinations were made on all elk and compared with the values obtained from captive elk. Similar values were noted in the captive and wild elk in calcium phosphorous ratio, glucose and total protein. Dissimilarity occurred with cholesterol, blood urea nitrogen,...

Serological studies in pigs with Mycoplasma hyopneumoniae

Further work is described on the complement-fixation (CF) test for Mycoplasma hyopneumoniae infection in pigs, using unheated pig serum. Young pigs, 7 weeks old, were more susceptible than older pigs to M. hyopneumoniae infection; they developed lung lesions and a positive CF reaction. Three out of eight 14-week-old pigs inoculated with M. hyopneumoniae did not produce a positive M. hyopneumoniae CF reaction. Serum samples from M. hyorhinis infected pigs produced slight reactions in the M. hyopneumoniae CF test. The CF reactions between sera from M. hyorhinis infected pigs and M. hyopneumoniae antigen were greater if lung lesions were present in the pig. The possible nature of these cross-reactions and the specificity of the test is discussed. One hundred and twenty five samples from the laboratory herd gave negative results in the M. hyopneumoniae CF test. Heating the pig serum had the effect of substantially decreasing the CF titres and the addition of 1 50 normal serum from day-old pigs did not fully restore the titres. Formalin had the effect of reducing and often eliminating the CF titres of both heated and unheated serum samples. Using gel diffusion studies M. hyopneumoniae antigen could not be detected in diseased lungs resulting from M. hyopneumoniae infection. A slide agglutination reaction could not be demonstrated using serum samples from M. hyopneumoniae infected pigs. The CF test showed that the strains of M. hyopneumoniae, 11, 6238, M244, EP29 and EP33, were antigenically similar. Cross-reactions occurred in the CF test between M. hyorhinis antigen and M. hyopneumoniae immune rabbit serum. Using gel diffusion studies these cross-reactions were shown to be due to adsorption of medium constituents by organisms when grown in broth. The immune rabbit serum contained antibodies to the medium's constituents.

Cardiovascular radiology in acute and chronic Chagas' myocardiopathy: Morphologic and dynamic study of the cardiac contour correlated with the histologic changes observed in myocardiopathies attributed to Schizotrypanum cruzi

The cases of 26 patients with Chagas' myocarditis have been analyzed with regard to the relationship between the x-ray changes, stage of the disease, and pathologic changes. Eight of these patients were seen during the acute stage of the disease, and 18 during the chronic stage. All of the patients with the acute form of the disease had Schizotrypanum cruzi in the peripheral blood. Two patients died. Nests of Leishmania within the myocardial fibers were found at autopsy. From a series of 53 autopsies of patients with chronic Chagas' myocarditis and a positive complement fixation reaction to Schizotrypanum cruzi, 18 cases were selected for study (all of these patients were under 30 years of age). They showed histologic changes of varying degree consistent with a diagnosis of chronic myocarditis. The morphologic and dynamic data of the cardiac contour were analyzed, and the electrocardiogram provided an accurate outline of the projection of each ventricle onto the chest wall. The pathologic findings were correlated with the radiologic and kymographic findings. In acute Chagas' myocarditis the increased size of the cardiac shadow and the decreased amplitude of the cardiac pulsations are related to the severity of the inflammatory process. The altered morphology and cardiac dynamics seem to be related to the cellular infiltrate and the inflammatory edema of the myocardium. In chronic Chagas' myocarditis there is a close relationship between the intensity of the myocardial fibrosis, cardiac enlargement, and the decreased motility of the heart. The increase in the length of the myocardial fibers and the myocardial fibrosis are seemingly responsible for these findings.

Behçet's syndrome and autoimmunity.

The aetiology of Behcet's syndrome has long been disputed. Beh?et (1937) first suggested a viral hypothesis on the basis of finding inclusion bodies in scrapings from the ulcers. Sezer (1953, 1956) claimed to have isolated a virus from these patients and to have reproduced the disease, and showed a strongly positive complement-fixation reaction in other patients with Behcet's syndrome. Evans et al. (1957) also grew a virus, and they showed the presence of neutralizing antibodies in the serum of patients with this disease, but not in control sera. Recently Mortada and Imam (1964) also grew a virus from one patient, but numerous other workers have failed to do so. The literature has been reviewed by Dudgeon (1961) and Dowling (1961). Oshima et al. (1963) and Shimizu et al. (1965) have raised the possibility that an autoimmune mechanism may play a part in the pathogenesis of Behcet's syndrome. They showed con vincingly in a large series of patients that there is a rise of serum globulin and sialic acid. They have also demonstrated the presence of autoantibodies against oral mucosa by the tanned red cell haemagglutination technique. In an immuno fluorescent investigation they claim to have shown significant fluorescence of the cytoplasm of peripheral blood leucocytes and of cells from the oral ulcers. While evidence of an auto immune reaction does not disprove the viral hypothesis it could be important not only from the aetiological point of view but also in understanding the pattern of the disease and of its response to treatment. The aim of this investigation was to carry out the haem agglutination, complement-fixation, and Ouchterlony's precipita tion test against foetal oral mucosa in 21 patients with Behcet's syndrome, as described by Lehner (1964, 1965) for a series of patients with recurrent oral ulc?ration. Furthermore, an attempt was made to differentiate the oral ulcers in Behcet's syndrome and to compare them with those of recurrent focal oral ulc?ration.

Study of autoimmune serologic reactions to ocular melanoma.

Immunologic aspects of human cancer have been of intermittent interest for several decades, and the Immunologic approach to the study of malignant disease has been regarded alternately with optimism and skepticism. Recently, autoimmune responses to specific tumor antigens in patients with malignant neoplasms have been investigated by several groups of workers. For example, in 1958 Grace and Kondo reported local inflammatory reactions surrounding tumors in eight patiients.¹Sera from these eight patients gave positive complement fixation reactions with alcoholic extracts of the malignant tissue. Graham and Graham have used the complement fixation test to demonstrate the presence of circulating antibodies in 12 of 48 patients with malignant disease.²In a later study, they prepared autogenous vaccines from tumors of 232 patients in the hope of increasing resistance to malignant tumors.³Failure to show local reaction to the vaccine was regarded as an unfavorable clinical sign, apparently indicative

Problem of positive complement-fixation reactions with the Reiter treponeme in the absence of syphilis. Role of a polysaccharide antigen.

Problem of positive complement-fixation reactions with the Reiter treponeme in the absence of syphilis. Role of a polysaccharide antigen.

Serologic Studies on Subclinical Melioidosis

Summary Of 337 sera from apparently healthy adult Thai males, 8.3% gave positive complement fixation reactions for melioidosis. Only 1 of 78 sera from Thai females was positive. None of 138 sera from a control group in the United States was positive with this test. Of 405 Thai sera, 29.1% gave positive hemagglutination reactions for melioidosis with a purified polysaccharide antigen. Only 7.4% of the control group in the United States gave positive reactions with this test. The protein antigen used in similar hemagglutination tests was not suitable for diagnostic purposes because positive reactions, apparently not referable to melioidosis, were encountered with this antigen in some sera. The combined results of the serologic survey indicated that subclinical or unrecognized mild melioidosis was probably rather prevalent in Thailand and that the 95% mortality figure for melioidosis as reported in the literature was not tenable. The significance of the serologic results in relation to the epidemiology of melioidosis is discussed.

Pathologic and Some Diagnostic Features of Histoplasmosis in Patients Entering a Missouri Hospital Final Report

Pathologic and Some Diagnostic Features of Histoplasmosis in Patients Entering a Missouri Hospital Final Report

Complement fixation test in experimental clinical and subclinical melioidosis.

Nigg, Clara (University of California, Berkeley), and Margaret M. Johnston. Complement fixation test in experimental clinical and subclinical melioidosis. J. Bacteriol. 82:159-168. 1961.-Soluble stable antigens prepared from Pseudomonas pseudomallei gave 4+ complement fixation reactions in a dilution of 1 to 8,000 when tested with specific rabbit antiserum diluted 1 to 10,000. The complement fixation reaction was positive in 100% of experimentally infected rabbits 9 to 11 days postinfection. Infected guinea pigs and monkeys showed similar results. Monkeys inoculated with very small infecting doses of P. pseudomallei developed positive complement fixation reactions in the absence of clinical manifestation of infection. An anamnestic complement-fixing antibody response could be induced in such monkeys, after the titer had dropped to approximately the preinfection level, by inoculating very small doses of viable P. pseudomallei or larger doses of killed melioidosis vaccine. The complement fixation test described appeared to be both sensitive and specific, and should be of value in human melioidosis which cannot be diagnosed on the basis of clinical manifestations alone. It is suggested that subclinical infections may play a role in the epidemiology of human meliodosis. The potential application of the complement fixation test to serological surveys in areas where melioidosis occurs endemically is discussed.

The Use of Purified Antigens in the Diagnosis of Clonorchiasis Sinensis by Means of Intradermal and Complement Fixation Tests

The limited research which has been conducted on the immunodiagnosis of clonorchiasis has yielded equivocal results. Chung and his coworkers used a saline extract of the adult worms in the intradermal and complement fixation tests. Two clonorchiasis and 18 paragonimiasis patients tested with this antigen showed a dermal sensitivity (Chung et al, 1955). The sera from 3 clonorchiasis and 25 paragonimiasis patients gave a positive complement fixation reaction (Chung et al, 1956). The intradermal test with a crude antigen was carried out in 136 infected individuals and 58 negative controls with unsatisfactory results (Hunter et al, 1958). Wykoff (1958) was able to detect antibody response in infected rabbits by the use of an ether extraction of the worms in the complement fixation test. However, even with this antigen, pre-infection rabbit sera reacted to some degree and antibody response had to be evaluated on a relative basis. These few reports based on limited experimentation suggested that further work on this problem was needed, with increased efforts toward the purification of the antigens. Therefore, the experiments reported in this paper were carried out.

A note on typhus in Egypt and the Sudan.

Summary 1) Complement-fixation tests with a soluble typhus antigen on sera collected from the indigenous population at various localities in Lower (Nile Delta) and Upper Egypt and the Southern Sudan revealed positive reactors in all three regions sampled. The highest percentage of positives was found in Lower Egypt (19.3), the next highest in Upper Egypt (13.2) and the lowest in the Southern Sudan (3.7). 2) The rate of positives increases with the age of the donor. 3) By utilizing specific epidemic and murine complement-fixing antigens, 35 of 50 current typhus infections were found to be of the epidemic type and 15 of the murine type. 4) A high percentage (34%) of 116 rodents captured at Alexandria gave a positive complement fixation reaction, but none of 146 rodents captured in a village in the Nile Delta was positive. 5) Though, since 1947, typhus has been at a low ebb—less than one case reported per 100,000 population—both louse-borne and murine typhus continue to occur, and in view of a growing-up, non-immune population and a developing resistance of the Egyptian lice to DDT, the danger, under favoring conditions, of epidemics in the future should not be ignored.

Complement-fixing antigens in concentrates of streptococcal culture supernates.

Summary1. Supernates of cultures of β-hemolytic streptococci were concentrated with respect to macromolecular material present. Such concentrates gave positive complement-fixation reactions with sera of rabbits which had been given courses of injections of living streptococci, and with sera of human subjects. 2. Evidence was obtained that complement-fixing antigenic material in such preparations was not identical with the complement-fixing fractions obtained from streptococcal cells, and complement fixation was probably not due to any of a number of the extracellular enzyme-antigens which can be found in streptococcal culture supernates.

Studies on the Prevention of Mumps

Summary The results of over 1800 skin tests and over 1500 complement fixation tests have been analyzed in terms of past mumps infection, age of the individual and geographical area. Correlation between past known infection and positive complement fixation or skin tests was of the order of 70 to 80%. With the skin test it was somewhat higher in the adult than in individuals less than 18 years of age, whereas the reverse was noted with the complement fixation test. Neither a positive complement fixation reaction nor a positive skin response affords absolute assurance of resistance to mumps but the incidence of infection among such individuals was found to be less than 2%, whereas it was many times that in those giving negative reactions. Since discrepancies between the results of the 2 tests, when performed simultaneously, were not infrequent, it is obvious that both technics should be employed to attain maximal accuracy in determining the immune status of an individual.

Studies on Lymphogranuloma Venereum Complement-Fixing Antigens

Summary A high percentage of serums from patients in the early stages of syphilis gave complement fixation reactions with phenolized boiled antigens prepared either from yolk sacs infected with lymphogranuloma venereum or from normal yolk sacs. Such nonsepcific reactions preclude a serological diagnosis of lymphogranuloma venereum. The nonspecific reactions observed with syphilitic serums were completely eliminated by using phenolized boiled supernate-antigens. Phenolized boiled supernate-antigens prepared from yolk sacs infected with lymphogranuloma venereum also gave positive complement fixation reactions with the serums of patients recovered from psittacosis and ornithosis. These cross reactions emphasize the close antigenic relationship within the psittacosislymphogranuloma venereum group of viruses.

The Complement Fixation Reaction in Toxoplasmic Infection

A frozen and thawed extract of toxoplasma-infected rabbit brain (but not similar extracts of certain other heavily parasitized tissues) yielded an antigen which fixed complement specifically in the presence of immune sera from experimentally infected rhesus monkeys but not rabbits, dogs, and cats. This complement fixing antibody appeared within 1 to 4 weeks after inoculation, but unlike the neutralizing antibody disappeared again in most monkeys, sometimes as early as 2 months. A certain number of human beings who were known or suspected to have experienced toxoplasmic infection also gave positive complement fixation reactions. However, twenty selected individuals whose sera had neutralizing antibodies against toxo-plasma gave negative complement fixation reactions, but in none of these was there evidence of recent or active infection. While a positive complement fixation reaction does not in all cases indicate active or even recent infection, it is believed that this test may have its greatest usefulness in the rapid diagnosis of active toxoplasmosis.

Vaginal trichomoniasis: Complement fixation, puerperal morbidity, and early infection of newborn infants

Examination of fresh vaginal discharge is the more practical and economical way to diagnose the presence of Trichomonas vaginalis. Cultures are highly satisfactory but add little to the study.Approximately 50 per cent of women infected with T. vaginalis gave positive complement fixation reactions, which were noted less often in carriers than in women with vaginitis. One-sixth of women in whom Trichomonas vaginalis could not be demonstrated also gave positive reactions. It is not improbable that some of these women had been previously infected.Trichomonas vaginalis infection is not associated with an increase in puerperal morbidity and its presence does not constitute an indication for treatment in asymptomatic patients.Approximately 5 per cent of female babies born to infected mothers were shown to be infected with Trichomonas vaginalis during the first eight days of life.

Specific Nature of Complement Fixing Antibody in Malaria as Demonstrated by Absorption Tests

We have confirmed the demonstration by Coggeshall and Eaton of a specific complement fixation reaction in malaria employing P. knowlesi antigens. The parasites were washed as free as possible of hemoglobin and other blood constituents and dried in vacuo. When ready for use a standardized amount was rehydrated with physiological saline, frozen and thawed, and the supernatant fluid used as antigen. We have tested sera from 83 patients in whose blood malaria parasites were demonstrated. Seventy-two percent gave a positive complement fixation for malaria at some time during the course of the disease. The positive reaction was correlated with the presence or recent presence of demonstrable parasites but not with the number of parasites. Our results show that a positive complement fixation reaction with our parasite antigen is probably diagnostic of malaria. However, a negative reaction does not rule out malaria. Sera from 134 individuals presumably free from malaria yielded 127 negative and 7 weakly positive reactions read as 1+ or ±. Forty-three of these sera were known to give a positive Wassermann reaction, 40, a negative Wassermann. One in each group gave a weakly positive reaction with the malaria antigen. It would appear that syphilis does not provoke non-specific reactions with the malaria parasite antigen. We have further shown that Wassermann negative patients who received induced malaria remained Wassermann negative throughout the course of their treatment, even after they had developed a strongly positive reactivity for the malaria antigen. Absorption experiments also indicate distinct and unrelated antibodies since treatment of serum with either the malaria or Wassermann antigen removes the specifically reacting substance from that serum without modification of its ability to fix complement in the presence of the other antigen. For these absorption experiments sera giving 4+ reaction with both the malaria and Wassermann antigens were used.

The Complement Fixation Reaction for Amebiasis: Comparative Tests Performed by Two Laboratories 1

SummaryThe serums of ninety patients observed at either The Mayo Clinic or the Vanderbilt University Hospital, all harboring Endamoeba histolytica, were tested for complement fixation with a variety of amebic antigens. The serums were examined independently in the laboratories of two institutions. There was general agreement in the findings of the two laboratories, but owing to the use of multiple antigens one laboratory was able to obtain more positive reactions than the other. Considering only tests which resulted in strong fixations found in either laboratory, twenty-nine of the ninety cases, or 32 per cent, gave positive complement fixation reactions. The average sensitivity of all tests now reported in the literature is 68 per cent. The two laboratories failed to check in 16.7 per cent of the tests. Cases of acute amebiasis gave a distinctly higher percentage of positive results than any other group of cases, but there were cases in which tissue was demonstrated to have been invaded by Endamoeba histolytica in which the reactions were negative. A considerable improvement in the preparation of antigen will be necessary before the test can be generally adopted.

Observations upon the Complement-Fixation Test in Monkeys Infected with Endamoeba histolytica

ConclusionIt is concluded that the results of these experimental infections with E. histolyticu in M. rctesus monkeys demonstrate that in these animals typical lesions of amebiasis occurred in the intestine and that a positive complement-fixation reaction for amebiasis followed each experimental infection.