Mitochondrial Antigens Research Articles

Immunological aspects of exposure to emissions from burning coal of high beryllium content

An epidemiological study was conducted on groups of people exposed occupationally (45 persons) and nonoccupationally (36 persons) to the combustion products of coal containing a comparatively high concentration of beryllium. The concentration of beryllium in the working atmosphere ranged between 30 and 800 × 10 −5 mg × m −3; in the town S, dwelling place of a nonoccupationally exposed cohort between 0.39 and 1.68 × 10 −5 mg × m −3. A group of 100 subjects who had no occupational contact with beryllium and other industrial toxic agents, and lived outside of the polluted region served as control cohort. In all examined persons the main classes of immunoglobulins and autoantibodies (lung, heart, liver, spleen, thyroid gland, suprarenals, and native DNA) and antibodies against nuclear (ANA) and mitochondrial (AMA) antigens (obtained from the lungs of intact and of experimental berylliosis rats) were determined. In both exposed groups elevated levels of IgG and IgA and increased concentrations of autoantibodies were found in comparison with the control cohort of people. Specific AMA and ANA were also found in both the exposed groups, with higher values in women. The demonstrated immunological changes in humoral immunoreactivity might be considered as signs of beryllium exposure. In the discussion the authors emphasize the increasing importance of immunological aspects in the study of environmental pollution.

Leukocyte migration test in subacute thyroiditis: hypothetical role of cell-mediated immunity.

There has been a paucity of data employing the leukocyte migration test (LMT) in regard to the role of cellmediated immunity (CMI) in subacute thyroiditis (ST). This has induced us toinvestigate the presence of CMI against subcellular components of human thyroid cells in patients with ST. These subcellular components obtained by the ultracentrifugation method in sucrose discontinuous gradient are: 1) cell membranes, 2) microsomes, 3) membrane-bound ribosomes, 4) mitochondria, and 5) nuclei. Moreover, a crude thyroid extract (CTE) was also used. These subcellular components have been verified by electron microscopy. The LMT technique of Soborg and Bendixen was performed in 22 patients manifesting positive thyroid autoantibody titers in the antithyroglobulin and/or antimicrosomal procedures in the course of their disorder as well as in 10 euthyroid students (volunteers). Different antigenic fractions were tested at the following concentrations [expressed as protein concentration (micrograms per ml) in 1 ml tissue culture medium] 1) membranes, 35 and 140; 2) microsomes, 85; 3) membrane-bound ribosomes, 125; 4) mitochondria, 100; 5) nuclei, 50 and 250; and 6) CTE, 40 and 80. Inhibition in the LMT test in patients with ST was observed using CTE [69 α 13 vs. 90 α 15 (controls); P < 0.001], nuclei (67 α 11 vs. 83 α 11; P < 0.001), microsomes (47 α 9 vs. 89 α 10; P < 0.001), mitochondria (60 α 6 vs. 78 α 7; P < 0.001), and ribosomes (52 α 13 vs. 85 α 20; P < 0.05). No difference from controls was in evidence when the thyroid cell membranes were usedas antigens (80 α 19 vs. 88 α 19; P = NS). The detection of CMI against nuclear, ribosomal, mitochondrial, microsomal,and crude thyroid antigens may well relate to a release of these fractions due to cytolysis brought about by viral infection and destruction.

Evidence that Adenosine Triphosphatase is One of the Mitochondrial Antigens of Autoimmune Liver Disease

Evidence that Adenosine Triphosphatase is One of the Mitochondrial Antigens of Autoimmune Liver Disease

Immunological Studies in Cattle Exposed to Polybrominated Biphenyls

The intactness of the immune system in cattle exposed to polybrominated biphenyls (PBBs) has been investigated by using several immunoassays. Eighty-seven animals have been studied, 35 control animals (not exposed to PBBs) and 52 animals exposed to PBBs (0.02–30 ppm/g fat equivalent). The immunoassays included a complete blood count, identification of peripheral blood T and B lymphocyte subpopulations, serum immunoglobulin levels (IgG, IgM, and IgA), the in vitro response to lymphocytes to phytolectins (PHA, Con A, PWM), the antibody response to Keyhole limpet hemocyanin (KLH), the cell-mediated response to PPD, and determination of autoantibodies and/or immunosuppressive serum factors. For control and PBB-exposed cattle, there was no statistical difference between the number of circulating erythrocytes or leukocytes, the hematocrit, or hemoglobin content; the percentage or number of T and B lymphocytes; the isotope incorporation index (DNA synthesis) of lymphocytes in response to mitogens; the concentrations of serum immunoglobulins IgG, IgM, or IgA; the mean peak titer to KLH; or in vivo or in vitro immune response to PPD. Additional evaluation of cattle with tissue levels of PBB greater than 3 ppm/g tissue for hematological and immunological parameters revealed no statistical difference from control animals. Other experiments were performed to evaluate serum from cattle exposed to PBBs for autoantibodies to smooth muscle, mitochondrial or nuclear antigens. No evidence for autoantibodies was observed. Further studies were done to examine the cytotoxic and/or immunosuppressive activity of sera from PBB-exposed animals. In these studies, the blastogenic response of lymphocytes from control cattle and humans were evaluated in the presence and absence of serum from animals exposed to PBBs (&gt; 3 ppm/g tissue). No evidence for either a cytotoxic or an immunosuppressive influence of such sera was demonstrable. Our studies indicate that PBB, at the levels studied, does not alter or interfere with lymphocyte surface antigens, the complex nuclear and cytoplasmic events required for mitosis and cell division, or the biological events required for antibody formation and cell-mediated immune reactions. Further, PBB exposure at the levels studied does not predispose cattle to autoantibody production or leucotoxic serum factors.

Chronic active hepatitis in patients with and without hepatitis B surface antigenemia.

This study was designed to compare the clinical and immunological characteristics of the hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative (cryptogenic) forms of chronic active hepatitis. The data of 48 patients with chronic active hepatitis, 24 with persistent HBs antigenemia and 24 without HBsAg, were analysed. HBsAg was detected by counter-immunoelectrophoresis and radioimmunoassay. The clinical features, biochemical liver function tests, immunoglobulins, complement C3, antoantibodies, and cell-mediated immunoreactivity of the two forms of the disease were compared. Cirrhosis was found to occur more frequently at the time of diagnosis in the HBsAg-negative group, and the serum alkaline phosphatase level was raised significantly compared to the HBsAg-positive form. The elevation of the IgG level was greater in the cryptogenic form, but the difference was not statistically significant compared to the HBsAg-positive patients. There was a marked difference in the frequency of the mitochondrial antibodies, but not of the antinuclear factor and other autoantibody-like serum factors. Lymphoblastic transformation revealed a similar diminution in response to phytohaemagglutinin stimulation in both groups of patients compared to the normal controls. An increase of the 3H-thymidine incorporation was seen after stimulation with human liver mitochondrial antigen, and leukocyte migration inhibition could be observed with this antigen in both forms of chronic active hepatitis.

Histopathological features in mixed types of chronic aggressive hepatitis and primary biliary cirrhosis. Correlations of liver histology with mitochondrial antibodies of different specificity.

A histopathological study was carried out on 27 patients with chronic inflammatory liver disease and clinical and/or biochemical evidence of cholestasis who had either mitochondrial antibodies against mitochondrial antigen fractions of 1.19 density ("PBC antigen"; 14 cases) or of 1.13 density ("CAH-PBC mixed-type antigen"; 13 cases). For comparison, the liver biopsies of 17 patients with chronic-aggressive hepatitis (CAH) and antinuclear and/or anti-smooth muscle antibodies but without cholestasis and mitochondrial antibodies, were evaluated. The 14 patients with mitochondrial antibodies against the PBC antigen showed the typical histological features of primary biliary cirrhosis (PBC). The 13 patients with mitochondrial antibodies against the CAH-PBC mixed-type antigen had heterogenous liver alterations. In 11 cases highly active CAH and/or active postnecrotic cirrhosis (AC) were found both with augmented ductular proliferation. Some of these cases showed distinct criteria of PBC as early bile duct lesions or absence of regular bile ducts. The liver histology of one case corresponded to classical PBC; another case to chronic persistent hepatitis. The CAH-patients without cholestasis and mitochondrial antibodies only occasionally showed bile duct proliferation. In conclusion, a high correlation was found between mitochondrial antibodies against the CAH-PBC mixed-type antigen and highly active CAH or early AC with augmented ductular proliferation. This represents an overlapping of CAH and PBC. In contrast, the cases with antibodies reacting to the PBC antigen showed the slowly progressive liver changes of typical PBC.

Taurine conjugation of arylacetic acids in the ferret.

reactivity. As anti-mitochondria1 antibodies can bind complement we used a complement-fixation test. Results from preliminary tests were difficult to interpret. The Paracoccus membranes had strong anti-complementary activity, which had to be diluted out. Also the sera available from patients with primary biliary cirrhosis were themselves anti-complementary up to quite high dilutions. Nevertheless, the sera tested did appear to demonstrate complement-fixing reactivity against both mitochondria1 membranes and Paracoccus membranes when compared with the corresponding normal serum controls. Further tests will be necessary to confirm the specificity of the reaction between Puracoccus denitrificans and sera from subjects with primary biliary cirrhosis. Corresponding tests are also clearly desirable with membranes from other aerobes and from anaerobes such as Streptococcus faecalis. These studies should also be extended to sera of mice immunized with syngeneic mitochondria (Davey et al., 1975) and to mice immunized with bacterial membrane preparations. Confirmation of a cross-reaction between anti-mitochondria1 antibody and bacterial membranes could throw new light on the nature of the mitochondrial antigen, and might also have implications as to alternative origins of anti-mitochondria1 activity in sera in human subjects.

Heterogenicity of mitochondrial antibodies (author's transl)

Sera from 137 patients with mitochondrial antibodies were tested against two different mitochondrial antigens. The mitochondrial antibodies from patients with pseudo-lupus erythematosus (PLE antigen) reacted exclusively with antigen which sedimented on moving-zone centrifugation at a density of 1.10, and contained no antigenic activity when tested against sera from patients with primary biliary cirrhosis (PBC). Purified PBC antigen had no PLE antigen activity at a density of 1.19, and all sera from patients with autoimmune liver disease fixed complement with this fraction. Sera from 54 of 55 patients with PLE reacted with the antigen of the PLE-gradient fraction. But 71 patients with liver disease had no such uniform reaction: sera from 39 patients fixed complement only with the PBC fraction, whereas 32 reacted stimultaneously with both the 1.10 and 1.19 density gradient fraction. The latter pattern was especially found in patients with chronic active hepatitis in whom antibodies to smooth muscle and nuclei were frequently detected.

Insoluble particulate antigen(s) in cell-mediated immunity of autoimmune thyroid disease

Cell-mediated immunity (CMI) in patients with Graves' disease, chronic thyroiditis, and primary hypothyroidism was observed by assay of lymphocyte-mediated cytotoxicity (LMC) and leukocyte migration inhibition (LMI). Lymphocyte responsivity to phytohemagglutinin (PHA) is normal in these diseases. In the LMC assay, lymphocytes of patients in each category responded to the antigens of thyroid homogenates, but not to purified human thyroglobulin. Cytotoxicity is least in Graves' disease and most obvious in primary hypothyroidism. In the LMI assay, patients' lymphocytes responded to thyroid microsomal-mitochondrial antigens, but not to thyroid cell sap. Lymphocytes of Graves' disease patients also responded to liver microsomal mitochondrial antigens. The particulate antigens lost activity when solubilized by ultrasonication or KCL extraction. There is no correlation between the PHA responsivity of lymphocytes and thyroid function, or between CMI and serum antithyroid antibodies or thyroid size. Treated and untreated patients had similar evidence of CMI. These data indicate that function of thymus-derived lymphocyte in vitro is not disturbed in autoimmune thyroid disease and that CMI against thyroid antigens can be demonstrated by assay of LMC and LMI. Insoluble particulate antigens appear more important than soluble antigens in CMI. LMC, presumably induced by soluble cytotoxic factor, “Lymphotoxin,” may play an important role in the progress of the autoimmune thyroid disease to hypothyroidism.

The intracellular distribution of polyribosomes synthesizing mitochondrial proteins

Mitochondrial proteins are shown to be coded for by nuclear genes and by mitochondrial DNA (mtDNA) while their synthesis is known to occur on both cytop lasmic and mitochondrial ribosomes (see [ 1,2] ). However the structural and functional interrelations between these translation systems within a cell as well as the contribution of different intracellular polyribosome (PRS) classes to biosynthesis of mitochondrial proteins remain to be studied. We tried a new approach to this problem, which consisted of the identification of the PRS involved in the synthesis of mitochondrial proteins using iz51labelled antibodies against mitochondrial antigens. The data obtained demonstrate that the immunochemical appraoch is valuable in the identification and quantitation of cellular PRS synthesizing proteins of mitochondria, chloroplasts and other organelles having dual intracellular origin. Such an approach could be also considered as a preliminary step in the preparative isolation of these PRS and of corresponding mRNA’s. In particular, a membrane-bound cytoplasmic PRS fraction is described which is associated with mitochondria and engaged largely in the synthesis of mitochondrial proteins.

Schizophrenia and autoimmune serological reactions.

Middle-aged women with schizophrenia and two matched control groups drawn from a similar hospital environment and a normal population were tested for autoantibodies to nuclear, thyroid, gastric, smooth muscle, and mitochondrial antigens. Schizophrenic patients failed to show the association of antibodies considered to be characteristic of autoimmune disease. In the schizophrenic patients and hospitalized subnormal controls there was an increased prevalence of autoantibodies to nuclei of blood polymorphonuclear leukocytes. This could be attributed to chance or an effect associated with prolonged hospitalization. Our findings offer little support to the autoimmune concept of schizophrenia.

Serological and histological diagnosis of primary biliary cirrhosis.

A simple immunofluorescence test for antibody to a mitochondrial antigen present in many tissues is a reliable method of distinguishing most cases of primary biliary cirrhosis from jaundice due to extrahepatic biliary tract obstruction. Of 30 cases diagnosed as primary biliary cirrhosis, 26 had antimitochondrial antibody whereas none of 77 cases with jaundice due to extrahepatic bile duct obstruction showed this serological abnormality. The antibody was also found in the serum of three of 42 patients who had other forms of cirrhosis and in two of 266 patients with no evidence of liver disease.Clinical, biochemical, and serological findings favour the view that primary biliary cirrhosis is a real entity which, in our present state of knowledge, cannot be defined clearly by any single method of investigation. In particular, the liver may show a variety of histological appearances which, interpreted without regard to the other features of the case, may lead to errors in diagnosis.

Comparative immunological studies in liver diseases.

By fractionation of human liver tissue, nuclear, mitochondrial, and connective tissue antigens were prepared. According to the results of serological tests, in conditions associated with substantial damage to the hepatic parenchyma, antibodies reacting with the nuclear and mitochondrial antigens are produced that show practically no reaction with the connective tissue antigen. It is advisable to use fractionated, connective tissue-free antigens for the demonstration of antibodies formed against liver tissue. The use of antigens containing connective tissue may lead to non-specific reactions.

Anticytoplasmic auto-antibodies in a patient with signs of tumour resistance

It is postulated that tumour antigens might not only lead to tumour resistance but also to induction of auto-antibody formation to normal tissue constituents. The only patient in our series of 195 breast cancer patients with heavy infiltration of lymphocytes and plasma cells into tumour and metastases, who is living well for longer than 17 years, appeared to be also the only patient with high-titered auto-antibodies to a non-organspecific cytoplasmic component (probably a mitochondrial antigen).