[Glafenin intolerance without any evidence of immunologic mechanism, a case report (author's transl)].
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Biomedical subjects
Publications and source records attributed to J C Homberg.
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About 0.1% of the sera in human pathology produce a peculiar, cytoplasmic, non-organ- and non-species-specific fluorescence. This may easily be differentiated from the already described anti-organelle antibodies and, more particularly, from the mitochondrial antibodies of primary biliary cirrhosis. Should rat tissues be used in the immunofluorescence test, fluorescence predominates over the first two portions of the renal proximal tubules (P1 and P2) and the mucous neck cells of the stomach. This pattern may be atrributed to mitochondria, and in particular to their inner membranes by fluorescent staining of the ellipsoid region of the rods and cones of the eyes, and by absorption with purified organelles. To distinguish this antibody from the already described mitochondrial antibodies, this one will be called mitochondrial antibody number 5 (M5). The seven carriers of this antibody suffer from systemic lupus erythematosus or autoimmune haemolytic anaemia. In these cases no diseases of the liver were observed, contrary to other classical mitochondrial antibodies.
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The D-penicillamine (D-Pen.) treatment can induce some diseases accompanied by autoantibodies: lupus, pemphigus, myasthenia. The authors present the results of a systematic study of autoantibody occurrence during D-Pen.-treatment of the rheumatoid arthritis (RA): (1) Anti-nuclear antibodies are slightly positive in 34% of the untreated RA. They appear or enhance in 44% of the treated patients (22/50). They reach high titers (1/500) in two clinical-induced lupus and in three asymptomatic cases. (2) Anti-native DNA antibodies are not found in untreated patients. They become markedly enhanced in two clinical lupus as in three asymptomatic cases (3/50). (3) Anti-epidermal intercellular substance-antibodies are absent in non-treated as well as on pemphigus-free treated patients (0/40). They are slightly elevated in 5 induced pemphigus. (4) Anti-striated muscle antibodies are absent in non-treated patients, rarely and moderately elevated (3/40) in the asymptomatic D-Pen.-treated group. These findings could have a practical interest for the survey of the treatment.
A monoclonal IgM (IgM) was found to react with stored human red blood cells (SHRBC) and human low density lipoprotein (LDL). IgM Re Fab fragment was reactive. SHRBC antigen was present, in a hidden state, in all fresh human ABO erythrocytes studies; it was not present in fresh or stored animal RBC. Cross reactivity of SHRBC and LDL antigens against IgM Re and IgM Re Fab was demonstrated. In contrast with SHRBC antigen, LDL antigen has no species specificity and was also found in rabbit and rat LDL. Furthermore, cross-reacting soluble inhibitors were also found in human saliva, and in a small molecule fraction issued from human and rabbit serum. The IgM Re also reacted with human and animal glomerular membrane. These findings are suggestive of two closely related but not identical antigens: a human specific SHRBC antigen and a LDL-associated, SHRBC-like antigen, which is a secreted, non-human specific substance. The former is part of the human RBC structure, the latter is a soluble molecule which may be found in saliva and in serum where it may be free or bound to LDL; it also binds to glomerular membranes.
The authors present 5 cases of pemphigus induced by D-penicillamine in a series of 180 cases of rheumatoid arthritis treated with this medication. In addition, anti-epidermal intercellular substance antibodies were sought in 40 asymptomatic patients. No antibodies were found in this group. The notion of induced pemphigus seems well established, as is the value of testing for antibodies in the surveillance of D-penicillamine treatment.
One case of Waldenström's macroglobulinemia is reported, in which the monoclonal IgM has an antibody activity against stored red cells, beta-lipoproteins and mammalian glomeruli. The antibody activity is observed with the purified IgM molecule, which cross reacts with the three antigens, and with the Fab piece. The study of the cross reactions shows that the antibody recognizes similar rather than identical antigens. This observation is to be added to the few cases already published of antibody against stored red cells, and of Waldenström's macroglobulinemia with antibody activity. The physiopathology of the occurrence of a M component with such an activity is discussed.
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A high titre cold autoagglutinin with anti-B specificity was found in the serum of an A1B group individual. It was associated with a low titre anti-I. This anti-B agglutinated most cells having a B antigen (normal B, A1B, A2B, from adult and cord bloods, B3), but failed to agglutinate Bx Cis-AB and Bh cells. Nevertheless, all these cells absorbed the anti-B SER at low temperatures. Fixation elution tests were also positive on the patient's cells and three consecutive absorptions on these cells completely removed the anti-B activity. The Coombs test was positive with anti-complement anti-globulin when the cells were sensitized by the serum at 4 degrees C. It was negative when the cells were sensitized at 37 degrees C. The patient did not show any sign of haemolysis. The anti-B was a IgM Kappa. Its reaction with normal B cells had an enthalpy change of - 36-000 cal./mole, i.e. very different from O ANd A individuals, but similar to that of the erythrocytic I antigen - anti-i antibody reaction. Quantitative measurements showed the erythrocyte B antigen similar to that of control A1B cells.
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Five out of 200 patients taking rifampicin 900 mg twice weekly and three out of 91 patients taking rifampicin who attended an immunology clinic developed intolerance to the drug. Antibodies to rifampicin, which were found in most cases, decreased steadily after the end of treatment but were detectable for up to 16 months. The dose of rifampicin and the blood levels are predominating factors in the occurrence of reactions. Thus the dose should be reduced in patients in whom rifampicin blood levels rise abnormally. When it is important to continue rifampicin treatment despite intolerance antibody titres within 24 hours after administration of the drug must be measured to find when they are lowest, which determines the "unreactive period," and when a further dose may be safely given.
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