C O N T E N T SDescriptionAn isoantibody normally present in the serum of an individual that causes the agglutination of the red blood cells of another individual of the same species. Also called isoagglutinin. See AlsoDiscussionApparently, we do not start out in life with antibodies to opposing blood types. We are however genetically programmed to produce them, and within two weeks of life most infants are already becoming sensitized to opposing blood type antigens in their environment.
We manufacture anti-blood type antibodies throughout our life: A recent study of 644 Taiwanese subjects showed that synthesis of anti-A and anti-B could be demonstrated in most Taiwanese infants by 2-4 months of age, increasing progressively to reach adult levels at around 1 year of age. Peak levels were reached at between 3-10 years of age and then declined with advancing years, with individuals of 80 years of age and over showing reduced levels similar to those seen in 6- to 12-month-old infants.
It has been shown that our levels of the anti-blood type isohemagglutinins is rising: A French study showed that they are about about 50% higher in children today than was that found in 1929. The authors suggest that this increased immune reactivity of children observed presently may be due to the increase use of prophylactic vaccinations, and that the levels of anti-blood type antibodies can serve as a pretty good index of antibody immunity, especially in children in the first years of life.
The effect of modern immunizations increasing anti-blood type antibodies is valid. Several common vaccines have been shown to cause inadvertent spikes in anti-blood group antibodies. The best known of these is the common vaccine against Pneumoccal pneumonia (Pneumovax). Several years ago it was noted that the levels of anti-A antibodies increased in individuals who were either blood type O or B when they received this vaccine. It is unclear at this time whether it is the vaccine antigen of a contaminant which produces the spike in anti-A. Several variants of the influenza virus have been shown to increase anti-blood type antibodies, some so consistently that there lack of production in one case history was considered an aberration.
Although found predominantly in the blood, many people also have high levels of isohemagglutinins in their saliva and vaginal fluids. One study found that about 36 per cent of the saliva samples had opposing blood group antibodies in it. The amount of antibody appears to vary from one individual to another. Also, different racial groups appear to have different profiles: Some groups have higher incidences of people with Anti-A in their saliva; others anti-B. This is probably the result of local dietary differences.
As one of the premiere textbooks of physiology states: “It is difficult to understand how agglutinins are produced in individuals who do not have the respective antigenic substances in their red blood cells. However, small amounts of group A and B antigens are believed to enter the body in the food, in bacteria, or by other means, and these substances presumably initiate the development of anti-A or anti-B agglutinins.” -Guyton, Textbook of Medical Physiology A recent short article from the Mayo clinic website does a nice job of summing up why we produce these antibodies: “S. Breanndan Moore, M.D., a hematologist at Mayo Clinic, Rochester, Minn., describes the formation of these naturally occurring antibodies. "Let's say a child is born with type O red cells. The child will begin forming antibodies to type A and B red cell antigens as soon as she starts eating food, because the A and B antigens are actually found in some plants. So, as soon as the child starts eating plant food, she'll be exposed to those antigens and start making antibodies against them. Later, if the child is transfused with blood that's not type O, she'll destroy the new red blood cells in a process called hemolytic transfusion reaction." (http://www.mayohealth.org/mayo/9902/htm/bloodtyp.htm) This is a very provocative statement, no pun intended. Take a moment to contemplate the fact that one of the major immune reactions against non-self, one of the few that is genetically programmed, is the result of hundred if not thousands of tiny inoculations over the course of a child’s early life with substances in the diet that are chemically identical with getting the wrong blood type in a transfusion! Strangely enough, it has been reported that a blood type A diabetic receiving a pancreas-spleen transplant from a type O donor went into severe transfusion reaction after high levels of anti-A antibodies began to develop in his bloodstream. Apparently, the spleen went right on thinking that it was type O and continued to manufacture anti-A antibodies.
About ten years ago, I measured the levels of these anti-blood type antibodies in several people with a variety of physical ailments. Not surprisingly, in several illnesses characterized by auto-immune dysfunction or excess inflammation, the levels of these antibodies were often found to be sky high. This was especially true in: Rheumatoid arthritis Endometriosis Chronic ear infection Chrohn’s disease of the intestines Asthma Eczema Hives
Thus it is possible that for many people with these disorders, the up-regulation of their immune response, which is responsible for the inflammatory aspects of the condition, may have had as its cause an initial inoculation by some environmental challenge that possessed the antigenicity of an opposing blood type. Interestingly many of these disorders such as asthma are also characterized by inappropriate clumping or aggregation of platelets, which are very important with regard to clotting and wound healing. There is evidence that opposing blood group antibodies may interact with platelets when in high concentration.
Since they serve to protect against infection it is not surprising that the levels of isohemagglutins can increase in times of acute infection. This has been especially noted for individuals who are blood type O, who often dramatic increases in the levels of their anti-A and anti-B antibodies during infections. Paradoxically, in blood type B individuals their levels of anti-A antibodies tend to drop during times of acute infection. A finding that was particularly true of African type B’s.
Anti-A and anti-B isohemagglutinins levels appear to drop in other illnesses, including the childhood leukemias. Compared with healthy children, leukemic children had lower isohemagglutinin levels which were also found to be in phase with relapses of their condition. Children who remained in remission had no such depletion of their antibodies.
A complete lack of either anti-A or anti-B was noted in a blood type O patient during an acute crisis of their chronic leukemia.
In adult blood type B lymphoma patients it has been reported that the development of an anti-B antibody can occur, although this would appear to violate all inherent rules of the immune system which mandate that one does not make antibodies to one’s basic tissue antigens, a phenomena termed ‘Horror Autotoxicus.’ Apparently, this can occur as a result of the lymphoma mutating bone marrow cells to sufficiently ‘un-repress’ this control.
This phenomena (blood type B making an anti-B antibody) was also noted in the blood of two patients who presented with fever and hemolytic anemia. It appeared transiently and was shown to be and IgM antibody .
In patients with Hodgkin’s Disease, radiation therapy results in a highly significant fall in the isohemagglutinin levels.
A dysfunction in the manufacture of anti-A antibodies has been speculated as a reason that persistent and recurrent urinary tract infections are more common in women who are blood type B, non-secretors than in any other group. Gonorrhea, one of the most common sexually transmitted diseases and one with a proclivity for people who are blood type B has an easier time infecting type B’s when their levels of anti-A are low. Apparently, the anti-A antibody helps the monocytes of the type B immune system to adhere to the gonorrhea bacteria better,
Sera from sixteen group O subjects reporting either urticaria, history of anaphylaxis, endometriosis, eczema or asthma were evaluated for the presence of isohemagglutinin-A (anti-A) by saline titration and human specific murine antiglobulins IgG1-4. Especially high saline titers and strong antiglobulin reactions were noted with urticaria, endometriosis and anaphylaxis when plotted against controls. Urticaria and anaphylaxis were also found to correlate with the broadest spectrum of IgG subclasses, with IgG 2 and IgG 3 appearing most consistently. Polymorphic factors may factor in pathogenesis, as differences in "natural immunity" observed with group O individuals appear to result in a less restricted, poorly behaved response (when T-cell dependent) to substances possessing A-like antigenicity. From the age of six months normal subjects show "naturally occurring" antibody to non-self ABO antigens. These antibodies are largely IgM, but wider certain circumstances, particularly in group O, large amounts of "immune" IgG antibody may be produced. Almost thirty years ago, Rawson and Abelson (1) qualified physicochemical differences between isoanti-A,B and isoanti-A or B in attempting to explain the preponderance of group O women among mothers of infants with ABO hemolytic disease of the newbom. This observance, coupled with evidence that patients with acquired hemolytic anemias are more likely to belong to group O than to groups A or B, stimulated interest in further qualifying the differences between isohemagglutinin subclasses and bloodgroup. By a combination of chromatography and ultracentrifugation, they separated the isohemagglutinin and isohemolysins into molecular types (i) gamma I and 2-globulins with S7 sedimentation coefficients (IgG) and (ii) gamma 1 -globulins with S19 sedimentation coefficients (IgM). In general, isohemagglutinins of S7 class showed maximal activity (titration endpoint) in the presence of antiglobulin serum, whereas S19 isohemagglutinins; are maximally active in sodium chloride solution. IgM class antibodies, although having relatively low affinity for single antigenic determinants, bind with great affinity to antigens with multiple epitopes and are efficient agglutinating and cytolytic agents. Membrane bound monomeric IgM is the major antibody receptor used by B-lymphocytes to recognize antigen, a very potent initiator of classical complement ABO fixation, and an effective first line of defense against bacteremia. The major class of isohemagglutinins (anti-A, anti-B) and many of the "natural" antibodies to micro-organisms are usually IgM. These have been postulated to arrive out of inapparent microbial inununization,(2) or are acquired characteristics resulting from oral immunization with animal foods containing A and B antigens.(3) Moreover, under some circumstances, particularly in subjects of group 0, large amounts of "immune" IgG class anti-A and anti-B can also be produced. This heterogenicity of isohemagglutinin subclass, characteristic of group O, coupled with the wide spectrum of naturally occurring substances in the environment that possess blood group antigenicity, stimulated interest in investigating the activities of isohemagglutinins found in subjects of this blood group presenting with clinical symptoms of hypersensitivity, a correlation first advanced by Mourant,(4) who speculated that the presence of both anti-A and anti-B antibodies (in addition to a third hemolysin, anti-A,B) might render group O individuals more susceptible to allergic reactions. Anti-A1The anti-A of group B serum appears, from simple studies, to contain separable anti-A and anti-A1. In direct tests, group B serum agglutinates A1 and A2 RBCs, yet following adsorption with A2 RBCs, group B serum reacts only with A1 RBCs. If further tests are performed, the differences between A antigen expression on A1 and A2 rbcs appears to be quantitative rather than qualitative. Further adsorption of group B serum with A2 RBCs will remove all serum activity for A1 RBCs. T The apparent anti-A1 made by adsorption of group B serum can be thought of as a weakened form of anti-A. It reacts with A1 RBCs because they have more A antigen than do A2 RBCs. The sera of persons of certain weak subgroups of A may contain anti-A1 that is serologically similar to the anti-A1 of group B adsorbed serum. Adsorbed group B serum can be used at the practical level to differentiate the two common A subgroups. More frequently, however, anti-A, reagents are employed that are manufactured from the lectin of Dolichos biflorus. The lectin will react with A, and A2rbcs unless it has been diluted appropriately. Reagent anti-A, lectins have been diluted by the manufacturer to react with A but not A2, RBCs. Hemagglutinins in fungus extracts and their blood group specificityExp Clin Immunogenet 1995;12(4):223-231 Furukawa K, Ying R, Nakajima T, Matsuki T Department of Legal Medicine, Gunma University School of Medicine, Maebashi, Japan. A total of 833 fungi harvested from 1977 to 1994 were tested and 422 extracts (47.8%) produced hemagglutination of human red cells. The lectins in fungus extracts which showed blood-group-specific or related reactions were partially purified by ammonium sulfate precipitation and gel filtration on a Sephadex G-100 column. Anti-H-like agglutinins were found in extracts of Pleurocybella porrigens, Naematoloma sublateritium and Pholiota squarrosa. These extracts agglutinated strongly with human group O red cells and rather weakly with A and B cells. Anti-A agglutinins were found in extracts of Hohenbuehelia serotina, Paxillus panuoides, Melanoleuca melaleuca and Hygrophorus capreolarius. The extract of Clavulinopsis fusiformis contained anti-B agglutinin. The ABH reactivities of the extracts were cofirmed by an agglutination inhibition test with ABH secretor saliva and blood group substances from human gastric linings and by the destruction of inhibiting activity using blood-group-specific decomposing enzymes. L-Fucose was the most active inhibiting monosacharide of anti-H-like agglutinins. The reaction of anti-A agglutinins was strongly inhibited by N-acetyl-D-galactosamine. D-Galactose and raffinose and melibiose which contain alpha-galactosyl residues were potent inhibitors of C. fusiformis agglutinin. Links |
