warm antibody autoimmune hemolytic anemia

Introduction

Introduction to warm-antibody autoimmune hemolytic anemia The warm antibody type autoimmune hemolytic anemia, the autoantibody with an optimum reaction temperature of 35 to 40 ° C with red blood cells is called a warm antibody, and it can be further divided into an incomplete temperature antibody and a warm autolysin. The warm antibodies can be classified into IgG, IgM, and IgA3 according to their chemical structures; IgG warm antibodies can be further divided into IgG1, IgG2, IgG3, and IgG4 subtypes. According to statistics, simple incomplete thermogenic autoantibodies account for about 68.9% of all autoantibodies. The IgG thermostable antibodies are mainly IgG1 and IgG3, and IgG2 and IgG4 are rare. [ basic knowledge The proportion of illness: the incidence rate is about 0.004% - 0.009% Susceptible people: more common in women Mode of infection: non-infectious Complications: mental disorders associated with hyperthyroidism Myelodysplastic syndrome Hematoporphyria Lung cancer Hepatitis Children with paroxysmal nocturnal hemoglobinuria Gaucher disease

Cause

The cause of warm-antibody autoimmune hemolytic anemia

Self-factor (50%):

Warm antibody-type hemolytic anemia can be divided into two categories according to its etiology: unexplained (primary) and secondary. Lymphatic proliferative diseases are the most common cause of secondary thermo-antibody AIHA, accounting for half. about,

Immunological factors (40%):

Followed by autoimmune diseases, the primary diseases of secondary temperature antibody type AIHA include all hematopoietic tumors (such as leukemia, lymphoma, myeloma and unexplained macroglobulinemia), connective tissue diseases (such as the system) Lupus erythematosus, scleroderma, rheumatoid arthritis),

Infection factor (10%):

Infectious diseases, especially children with viral infections, immune diseases (such as hypogammaglobulinemia, abnormal globulinemia, immunodeficiency syndrome), gastrointestinal diseases (such as ulcerative colitis) and benign tumors (such as ovaries) Dermoid cyst),

Petz collected 656 cases of warm antibody type AIHA from 1956 to 1973, of which only 292 cases (45%) were primary, and 364 cases (55%) were secondary. In recent years, there have been reports of hyperthyroidism and abnormal myelodysplasia. Syndrome, hematoporphyria, lung cancer, acute severe hepatitis, paroxysmal nocturnal hemoglobinuria and Gaucher disease with AIHA.

Pathogenesis

1. The mechanism of production of anti-erythrocyte autoantibodies has not been elucidated, and the possible factors are as follows.

(1) Viral infection can activate polyclonal B cells or chemicals to bind to erythrocyte membranes: altering their antigenicity and the like may result in the production of autoantibodies.

(2) Lymphoid tissue can cause the body to lose its immune surveillance function due to infection, tumor and immune deficiency: it can not recognize its own cells, which is conducive to the production of autoantibodies.

(3) T helper cell (Th) balance disorder: Th2 hyperfunction, mainly produces IL-4, IL-6 and IL-10, activates B lymphocytes to make their function abnormally hyperactive, producing their own red blood cell antibodies.

2. The destruction form and mechanism of AIHA red blood cells

(1) Extravascular red blood cell destruction: mainly found in warm antibody type AIHA, erythrocyte membrane is sensitized by adsorption of IgG, incomplete antibody sensitized red blood cells are not enough to immediately destroy blood vessels and hemolyze, but can be repeated by macrophages Phagocytosis and hemolysis, there may be 1 × 106 IgG Fc receptor (FcR) on the macrophage membrane, which increases or decreases with the activity of macrophages. There are three types of receptors: FcRI, FcRII and FcRIII, and FcRI is almost all Occupation of monomeric IgG in plasma, FcRII binds to dimeric IgG, only FcRIII plays an important role in IgG3 and IgG1 (IgG3>IgG1), but does not respond to IgG2 and IgG4. The main reaction after binding of IgG1 to FcRIII is phagocytosis. However, IgG3 binds to FcRIII and is cytotoxic and finally destroys in the spleen. Patients with IgG3 have hemolysis signs, while only 65% of IgG1 alone have hemolytic reaction, so IgG3 is much more damaging to sensitized red blood cells. Other subtypes are severe, while IgG4 is almost unresponsive, and the rate of red blood cell destruction is not necessarily proportional to the amount of IgG adsorbed on red blood cells. Different cases have red blood cells that are sensitized by the same amount of IgG, and their survival periods are different.

When the red blood cells adsorbed with IgG3 or IgG1 meet with macrophages, the contact part is deformed and finally swallowed; sometimes only a part of the membrane is dragged and digested, and the membrane is defective, although it can repair itself, membrane protein and phospholipid After repeated loss of the substance, the red blood cells tend to be spherical, and eventually they are mainly blocked in the spleen and the C3b receptor is also on the macrophage membrane. If the erythrocyte membrane is sensitized by both IgG and C3, the spleen can be accelerated to destroy the red blood cells. .

The phagocytosis process of macrophages includes three stages of "recognition", "attachment" and "ingestion"; wherein "recognition" is mediated by IgG FcR and C3bR on the surface of macrophages, but "attachment" mainly depends on C3bR, and "Intake" relies mainly on IgG FcR. The "attachment" of C3b and the "intake" of IgG promote the macrophage effect and cause severe hemolysis, and the destruction site is mainly in the spleen.

Separately sensitized red blood cells, except that complement is activated by the immune complex away from red blood cells and binds to the erythrocyte membrane to cause intravascular hemolysis. It can also cause sensitized red blood cells to be destroyed in the liver because of the large volume of the liver, abundant blood flow, and macrophages. The number of cells is relatively higher than that of the spleen, but C3 extravascular hemolysis is generally mild, because it is only "attached" without ingestion and may not be swallowed.

Mononuclear phagocytic cells also have IgA FcR, so red blood cells sensitized by IgA are mainly destroyed in the spleen; for thermophilic IgM incomplete antibodies, mononuclear phagocytic cells have no corresponding receptors, IgM has activating complement, but warm IgM cannot Activation of whole complement can only reach the C3 stage, combined with the macrophage C3 receptor, and finally destroyed in the liver.

(2) intravascular hemolysis: common in paroxysmal cold hemoglobinuria, less common in cold agglutinin syndrome, but very rare in warm antibodies, intravascular red blood cell destruction mainly due to antibody activation of complement, caused by traditional methods of hemolysis The antibody (mainly IgM, rare IgG, IgG3 most active in IgG, followed by IgG1 and IgG2) binds to the antigen on the erythrocyte membrane, and the antibody structure mutates, causing the originally masked CH2 region located on the Fc segment. The complement junction is exposed to C1q (C1 consists of C1q, C1r, C1s). When C1q is bound, the structure mutates, revealing the active part of the enzyme, acting on C1s, and finally causing the C1 molecule to be activated (C1), followed by C3. Activation, cleavage to C3b, C5b and C6-9 are combined into a complex through a series of activation and cleavage, submerged in the erythrocyte bilayer lipid membrane, ion leakage occurs, especially potassium ions lose sodium ions into the cells, red blood cells swell So that hemolysis in the blood vessels.

Prevention

Warm antibody type autoimmune hemolytic anemia prevention

Pay attention to the reasonable combination of diet, such as eating some fruits after a meal, the fruit is rich in vitamin C and fruit acid, which can promote the absorption of iron. Drinking strong tea after a meal, due to the combination of iron and tannic acid in the tea to form a precipitate, affecting the absorption of iron. Cooking food in a wok is good for preventing anemia.

Complication

Warm-antibody autoimmune hemolytic anemia complications Complications Hyperthyroidism associated with mental disorders Myelodysplastic syndrome Hematoporphyria Lung cancer Hepatitis Pediatric paroxysmal nocturnal hemoglobinuria Gaucher disease

Warm antibody type autoimmune hemolytic anemia complicated by hyperthyroidism, myelodysplastic syndrome, hematoporphyria, lung cancer, acute severe hepatitis, paroxysmal nocturnal hemoglobinuria and Gaucher disease.

Symptom

Warm-antibody type autoimmune hemolytic anemia symptoms common symptoms diarrhea high fever dizziness shock cold war coma back pain immune hemolysis

The incidence is more common in women, especially in the primary, from infants to the elderly can be involved, it has been reported that 73% are over 40 years old, the clinical manifestations of this disease are diverse, different in severity, more chronic, acute onset Occurred in children, especially with infected people, occasionally in adulthood, rapid onset, chills, high fever, low back pain, vomiting and diarrhea, very serious symptoms, can have shock and nervous system performance, such as headache, irritability and even Coma, chronic onset can first have dizziness and general weakness, only a few months after the discovery of anemia, the degree varies.

Examine

Examination of warm-antibody autoimmune hemolytic anemia

1. Peripheral blood normal pigmented anemia, a large number of spherical cells can be seen on the blood film, 1/3 of the patients have a number of young red blood cells, occasionally red blood cells are phagocytized, reticulocytes are increased, and very few can reach 50%, more than half The number of white blood cells is normal, leukocytosis is increased in the acute hemolysis stage, and even leukemia-like reactions occur. The number of platelets is in the normal range, but thrombocytosis is the first.

2. The bone marrow image is hyperplasia, the young red blood cell proliferation is the main, the grain/red ratio is inverted, and the red blood cells in the course of the disease can be giant and young, but the serum folic acid and vitamin B12 are measured in the normal range.

3. Anti-human globulin (Coombs) test (abbreviated as AT) Direct anti-human globulin test (DAT) is a method for determining the insensitivity of incomplete antibodies and/or complements bound to erythrocytes, and is a more specific laboratory for diagnosing AIHA. Index, the Q potential of the erythrocyte membrane keeps a certain distance between the two red blood cells, the incomplete antibody (IgG) molecule is small, can not be grafted in two adjacent red blood cells, but can only be combined with one red blood cell antigen, with normal people Serum immunized rabbits, obtained anti-human globulin serum, anti-human globulin antibody is a complete antibody, can be combined with the Fc segment of multiple incomplete antibodies, play a bridging role to cause agglutination of sensitized red blood cells, due to immune serum Different, specific anti-IgG and/or anti-complement-specific Coombs serum can be prepared. According to the results of the Coombs test, the warm antibody type AIHA can be further divided into three subtypes: IgG type (20% to 66%), IgG+C3 type. (24% to 63%) and C3 (7% to 14%).

Although a small number of patients with AIHA have typical clinical manifestations and have a good effect on glucocorticoids, the Coombs test is negative, which may be false negative, and false negatives are seen in:

1 The number of IgG molecules bound to the erythrocyte membrane is less than 500;

2 The red blood cells are not sufficiently washed, and the suspension is mixed with serum non-warre antibody globulin (neutralized anti-human globulin);

3 Some warm antibodies have low affinity with red blood cells and fall into plasma. False positives are found in:

1 normal people cause red blood cells to be sensitized by C3 due to infection;

2 certain diseases (such as nephritis, PNH, etc.) increase the level of C3 in the body;

3 erythrocyte C3 receptor binds to circulating immune complexes;

4 Certain antibiotics (such as cephalosporins) cause red blood cells to non-specifically adsorb plasma globulin.

Free antibodies can sometimes be found in AIHA blood and can be identified by indirect anti-human globulin test (IAT) or trypsin-treated red blood cells, which often have severe hemolysis.

4. Other serum tests may be positive for Fahrenheit, serum gamma globulin increased, antinuclear antibody positive and C3 decreased.

Diagnosis

Diagnosis and identification of warm-antibody autoimmune hemolytic anemia

Diagnosis of warm antibody type AIHA is mainly based on: 1 whether there is evidence of extravascular hemolytic anemia; 2Coombs test is positive; 3 whether there is evidence of other hemolytic diseases; 4 whether adrenal cortical hormone immunosuppressive therapy is effective, if the first 2 All are "yes", the warm antibody type AIHA can be diagnosed. If the second item is "no", then the third item "no" is required, and the first and fourth items are "yes" to confirm the so-called "Coombs test negative". The warm-antibody type AIHA" has been proved by many people. This type of AIHA is mainly caused by the insensitivity of the traditional Coombs test method. If it is changed to a more sensitive method such as radioimmunoassay or immunolabeling, there will be about half of it. The "Coombs test-negative" patient is tested and has a warm-type antibody. In addition, the warm-type antibody AIHA can cause the red blood cells to be spherical due to the adhesion of the antibody to the surface of the red blood cells, so attention should be paid to hereditary spherocytosis (HS). Identification; HS may have a positive family history, but no warm type of auto-erythrocyte antibody, AIHA is vice versa; can also do sucrose hypertonic cold solubilization test, the test is HS positive, AIHA negative.

When the warm-antibody type AIHA is diagnosed, further possible causes should be sought, especially lymphocyte diseases, mononuclear macrophage system diseases, and connective tissue diseases and infectious diseases.

Was this article helpful?

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.