Pediatric X-linked hyperimmunoglobulin Memia

Introduction to X-linked high immunoglobulin Memia in children X-linked hyperimmune gamma (XHIM) is a rare primary immunodeficiency disease characterized by recurrent infection with serum IgG, IgA, IgE levels and IgM normal or Raise. basic knowledge The proportion of illness: the incidence rate is 0.0001% - 0.0004% Susceptible people: children Mode of infection: non-infectious Complications: Oral ulcers, stomatitis, thrombocytopenia, hemolytic anemia, hypothyroidism, malignant tumors

The cause of X-linked hyperimmune globulin M in children

Causes:

For a long time, HIM was considered to be an immunoglobulin conversion disorder caused by endogenous defects in B cells. It was not until 1983 that T cell defects were recognized. The inability to provide effective auxiliary information to B cells is closely related to the pathogenesis of HIM. In 1991, using monoclonal technology, it was found that XHIM is caused by the inability of T cells to express CD40L, CD40L, the gene is located at Xq26.3~27, 13 kb long, consisting of 5 exons and 4 introns interposed between them. Its expression product CD40 ligand (CD40L) belongs to the tumor necrosis factor (TNF) superfamily type II transmembrane protein and is mainly expressed in triploid form on activated CD4+ T cells.

A database of CD40L gene mutations has been established. Of the 75 mutations, 42 are single nucleotide substitutions in the coding region (mostly missense mutations), resulting in amino acid substitutions and premature transcription termination, insertion of other mutation types, and large gene deletions. The non-framework is missing, and the mutation hotspots are mainly concentrated in Exon No. 5. Xinhua Hospital of Shanghai Second Medical University recently discovered a CD40L gene point mutation in XHIM in China.

Pathogenesis:

The binding of CD40L to CD40 on B cells is a key signal for the production of memory B cells, which constitutes a germinal center, and promotes the conversion of IgM into IgG, IgA or IgE. T cells can bind to macrophages and dendritic cells CD40 via CD40L. It secretes IL-12 and forms an immune response to intracellular microorganisms.

The result of mutation of CD40L gene changes the crystal structure of CD40L protein, which makes it unable to effectively expose the binding site of CD40 molecule, or enhances the water repellency of this region, thus unable to bind to CD40 molecule, resulting in T cell-dependent antigen-re-immune response disorder. Therefore, patients are prone to bacterial, Pneumocystis carinii and Cryptosporidium infections.

Prevention of X-linked high immunoglobulin Memia in children

Pregnant woman health care

It is known that the occurrence of some immunodeficiency diseases is closely related to embryonic dysplasia. If pregnant women are exposed to radiation, receive certain chemical treatments or develop viral infections (especially rubella virus infections), they can damage the fetal immune system. Especially in the early pregnancy, it can affect multiple systems including the immune system. Therefore, it is very important to strengthen the health care of pregnant women, especially in the early pregnancy. Pregnant women should avoid receiving radiation, use some chemical drugs with caution, and inject rubella vaccine to prevent as much as possible. Virus infection, but also to strengthen the nutrition of pregnant women, timely treatment of some chronic diseases.

2. Genetic counseling and family survey

Although most diseases cannot determine the genetic pattern, genetic counseling for diseases with defined genetic patterns is valuable if genetically immunodeficiency in adults will provide the developmental risk of their children; if a child has autosomals Recessive genetic or sexually linked immunodeficiency disease, it is necessary to tell parents that their next child is likely to be sick, for patients with antibodies or complement deficiency patients should check the antibody and complement levels to determine the family disease For some diseases that can be genetically mapped, such as chronic granulomatosis, parents, siblings and their children should be genetically tested. If a patient is found, it should also be performed among his or her family members. Check that the child's child should be carefully observed at the beginning of the birth for any disease.

3. Prenatal diagnosis

Some immunodeficiency diseases can be prenatally diagnosed, such as cultured amniotic fluid cell enzymology can diagnose adenosine deaminase deficiency, nucleoside phosphorylase deficiency and some combined immunodeficiency diseases; fetal blood cell immunological test can be Diagnosis of CGD, X-linked no-gammaglobulinemia, severe combined immunodeficiency disease, thereby terminating pregnancy and preventing the birth of the child, this disease is a relatively rare disease, but early accurate diagnosis, early specific treatment and It is important to provide genetic counseling (prenatal diagnosis or even intrauterine treatment).

Pediatric X-linked high immunoglobulin Memia complications Complications Oral ulcers, thrombitis, thrombocytopenia, hemolytic anemia, hypothyroidism, malignant tumor

Repeated severe infections, gastrointestinal complications and malabsorption, persistent stomatitis and recurrent oral ulcers, thrombocytopenia, hemolytic anemia, hypothyroidism and malignant tumors.

Symptoms of X-linked hyperimmune globulinemia in children Common symptoms Skin and soft tissue infections Immunodeficiency stomatitis Repeated upper respiratory tract infections Oral ulcers Diarrhea Leukopenia Reduced thrombocytopenia Hypothyroidism

Infection

With the attenuation of antibodies from the mother, children with XHIM have repeated upper respiratory tract infections, bacterial otitis media and pneumonia from 6 months to 2 years after birth. Pneumocystis carinii pneumonia can be the earliest manifestation of the disease, gastrointestinal tract Symptoms and malabsorption are also common, Giardia and Cryptosporidium infection can cause persistent diarrhea, tonsil, skin and soft tissue infections are common, soft tissue infection around the trachea is often life-threatening, due to neutropenia caused by persistent stomatitis And recurrent oral ulcers.

2. Lymphoid hyperplasia and autoimmune diseases

The proliferation and enlargement of lymphoid tissue such as tonsil, spleen and liver is a common manifestation of XHIM. The appearance of autoantibodies is associated with thrombocytopenia, hemolytic anemia, hypothyroidism and arthritis.

3. Tumor

Lymphoid tissue tumors are the most common, accounting for 56% of XHIM-combined tumors; liver and biliary tumors can also occur, which is rarely seen in other primary immunodeficiency diseases.

Examination of X-linked hyperimmune globulin M in children

Immunoglobulin

Serum IgG, IgA, IgE deficiency or significantly decreased, in very few patients with elevated serum IgA and IgE, serum IgM levels are normal or up to 1000mg / ml, IgM polyclonal amplification, IgM increased and repeated and chronic stimulation, and Not a direct result of the CD40L defect, the T cell-dependent antigen (such as phage x174) antibody reaction shows that the IgM antibody response is reduced, no IgG antibody is formed, and after the B cell is stimulated by the antigen, the V-region mutation rate of the surface IgM is decreased, affecting the affinity thereof. Sex and specificity.

2. Peripheral blood T cells and B cells

Peripheral blood B cell number and expression membrane IgM, IgD normal, occasionally can simultaneously express IgM and IgG, do not express other types of immunoglobulin, total T cell number and subpopulation percentage are in the normal range, but T cell proliferation response is reduced.

3. Other inspections

50% of children present with persistent or periodic neutropenia, and 25% of children develop anemia and thrombocytopenia due to autoantibodies.

4.CD40L detection

The expression of CD40L on activated CD4+ T cells was detected by soluble CD40L receptor (CD40L) receptor or anti-CD40L monoclonal antibody. The negative expression of this molecule can be diagnosed as XHIM, and the neonatal T cell CD40L molecule is physiologically low. Such examinations should be performed after 19 to 28 weeks. The analysis of CD40L gene mutations can be used for the diagnosis of prenatal diagnosis and for the discovery of female disease carriers.

Auxiliary inspection

X-ray

Bacterial pneumonia, interstitial pneumonia or Pneumocystis carinii pneumonia can be seen.

2.B Ultra

Visible liver, splenomegaly and lymphadenopathy, or liver, biliary tumors.

Diagnosis and differential diagnosis of X-linked hyperimmune globulin M in children

The characteristics of clinical repeated severe infection, combined with elevated serum IgM and decreased IgG, IgA, and corresponding changes in peripheral blood can be confirmed.

Different from non-X-linked high IgMemia, its clinical manifestations are similar to XHIM, but the genetic characteristics are different, which is autosomal recessive or dominant inheritance.

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.