About 60%-90% of type I (insulin-dependent) diabetics have antibody against islet cell cytoplasmic glycoprotein (“islet cell autoantibody”) at the time of diagnosis, and many of those initially without this antibody develop it later. This antibody disappears within 2 years after appearance in 85%-90% of type I diabetics. It has also been reported in about 20% of type II diabetics and about 10% of gestational diabetics at time of diagnosis. About 30%-50% of children have autoantibody against insulin (antiinsulin antibody) at time of diagnosis before beginning insulin therapy and some (much less than formerly) develop it after using therapeutic insulin. Some patients have autoantibodies against beta cell surface antigen (beta cell antibodies). Over 95% of type I patients possess the human lymphocyte antigen (HLA) DR3 or DR4. However, at present these autoantibodies and HLAs are not being widely used in clinical medicine or in diagnosis.
Tag: Autoantibodies
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Autoantibodies
Autoantibodies present an interesting problem, both in their clinical manifestations and in the difficulty of laboratory detection and identification. They may be either the warm or cold type and may be complete or incomplete.
Warm autoantibodies react at body temperature and are most often of the incomplete type. They comprise about 70% of autoantibodies. They may be idiopathic or secondary to certain diseases. The main disease categories responsible are leukemias and lymphomas (particularly chronic lymphocytic leukemia and Hodgkin’s disease); collagen diseases (especially disseminated lupus); and, uncommonly, a variety of other diseases, including cirrhosis and extensive carcinoma. Results of the direct Coombs’ test are usually but notalways positive, both in the “idiopathic acquired” and the secondary autoimmune hemolytic anemias. In one report, 2%-4% of patients with autoimmune hemolytic anemia had a negative direct Coombs’ test result. If the Coombs’ test result is negative, demonstration of warm autoantibodies is very difficult, often impossible.
Cold autoantibodies react at 4°C-20°C and are found so frequently in normal persons that titers up to 1:32 are considered normal. Theyare hemagglutinating and are believed to be due to infection by organisms having antigenic groups similar to some of those on the RBCs. These antibodies behave mostly as bivalent types and require complement for reaction. In normally lowtiter they need refrigerator temperatures to attack RBCs. In response to a considerable number of diseases, these cold agglutinins are found in high titer, sometimes very high, and may then attack RBCs at temperatures approaching body levels, causing hemolytic anemia. High-titer cold agglutinins may befound in nonbacterial infections, especially mycoplasma pneumonia (primary atypical pneumonia), influenza, and infectious mononucleosis; in collagen diseases, including rheumatoid arthritis; in malignant lymphomas; and occasionally in cirrhosis. Fortunately, even when cold autoantibodies are present in high titer there usually is no trouble, and generally only very high titers are associated with in vivo erythrocyte agglutination or hemolytic anemia. This is not always true, however. The direct Coombs’ test result is usually negative. When cold agglutinin studies are ordered, an indirect Coombs’ test is generally done, with the first stage being incubation of RBCs and the patient’s serum at 4°C-10°C.
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Immunohematology: Antibody Detection, Blood Group Antigens, and Pretransfusion Tests
Before this subject is discussed, it is useful to give some definitions:
Antigen: Any substance that causes formation of antibodies to it. The most common antigens are protein, but certain carbohydrate polysaccharides may act in a similar manner. Lipid may be combined with either. Each antigen has a certain chemical configuration that gives it antibody-provoking ability. This specific chemical group may become detached from its carrier moleculeand temporarily lose antigenic power; it is then called a hapten. Attachment of a hapten to another suitable molecule leads to restoration of antigenic properties.
Antibody: Proteins of the globulin class, most often gamma globulins, produced by lymphocytes and plasma cells in response to antigenic stimulation. They may be specific, combining only with specific antigen molecules, or nonspecific, combining with a variety of antigens. Presumably, nonspecific antibodies attack a variety of molecules because similar hapten groups may be present even though the carrier molecule is different (cross reactivity).
Agglutinogen: Antigen on the surface of a red blood cell (RBC).
Agglutinin: Antibody that attacks RBC antigens and manifests this activity by clumping the RBCs.
Hemolysin: Same as an agglutinin, except that lysis of affected erythrocytes takes place.
Isoantibodies (alloantibodies): Antibodies produced against antigens coming from genetically different individuals of the same species. These “foreign” antigens are usually introduced into the body by transfusion or by pregnancy (if fetal RBCs containing antigens that the mother lacks reach the maternal circulation). When isoantibodies are produced, they do not cause disease unless RBCs containing antigens that the antibodies recognize subsequently come in contact with these antibodies.
Autoantibodies: Antibodies produced by the body against one or more of its own tissues. These antibodies are associated with autoimmune disorders and may cause clinical disease. There are several types of antibodies, depending on their occurrence and laboratory characteristics:
Complete (bivalent) antibodies: These usually will directly agglutinate appropriate RBCs. In vitro tests for these antibodies tend to demonstrate better reaction in saline medium at room temperature (20°C) orlower. They often require complement.
Incomplete (univalent) antibodies: These usually cannot directly agglutinate appropriate RBCs but only coat their surface. In vitro tests for these antibodies tend to show better reaction at higher temperatures, such as 37°C, and in high-protein medium.
Warm antibody: Reacts best in vitro at 37°C.
Cold antibody: Reacts best at 4°C-10°C.