Introduction:
X-linked hyper-IgM syndrome (XHIM)It is a rare primary immunodeficiency disease. The disease is characterized by recurrent infection with decreased levels of serum IgG, IgA, IgE and normal or elevated IgM.
Cause:
(1) Causes of the disease
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, XHIM was found to be caused by the inability of T cells to express CD40L. CD40L, a gene located at Xq26.3-27, 13 kb in length, consists of 5 exons and 4 introns interposed between them. The expression product CD40 ligand (CD40L) belongs to the tumor necrosis factor (TNF) superfamily. Type II transmembrane proteins, expressed predominantly in triploid form on activated CD4+ T cells.
A database of CD40L gene mutations has been established, of which 42 of the 75 mutations are single nucleotide substitutions (mostly missense mutations) in the coding region, resulting in amino acid substitutions and premature transcription termination. Other mutation types include insertions, large gene deletions, and non-framework deletions. The mutation hotspots are mainly concentrated in exon 5. Xinhua Hospital of Shanghai Second Medical University recently discovered a case of XHIM CD40L gene point mutation in China.
(two) pathogenesis
CD40L binds to CD40 on B cells and is a key signal for the production of memory B cells, which constitutes a germinal center, and promotes the conversion of IgM classes to IgG, IgA or IgE. T cells bind to macrophages and dendritic cells CD40 via CD40L, which induces the secretion of IL-12, forming 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.
symptom:
1. Infection With the attenuation of antibodies from the mother, children with XHIM develop 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 this disease. Gastrointestinal complications and malabsorption are also common, and Giardia and Cryptosporidium infection can cause persistent diarrhea. Tonsils, skin and soft tissue infections are common, and soft tissue infections around the trachea are often life-threatening. Persistent stomatitis and recurrent oral ulcers due to a decrease in neutrophils.
2. Lymphoid hyperplasia and autoimmune diseases The proliferation and enlargement of lymphoid tissues such as tonsils, spleen and liver are the common manifestations of XHIM. The appearance of autoantibodies is associated with thrombocytopenia, hemolytic anemia, hypothyroidism, and arthritis.
- Tumor lymphoid 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.
diagnosis:
The characteristics of clinical repeated severe infection, combined with increased serum IgM and decreased IgG, IgA, and corresponding changes in peripheral blood can be confirmed.
complication:
Repeated severe infections, gastrointestinal complications and malabsorption, persistent stomatitis and recurrent oral ulcers. It can cause thrombocytopenia, hemolytic anemia, hypothyroidism and malignant tumors.
treatment:
Infusion of IVIG at 500 mg/kg per month is important to reduce the frequency and severity of infection. If the child's response is poor, increase the amount and frequency of IVIC infusion. In order to prevent complications such as bronchiectasis, serum IgG levels should be kept at a high limit in the normal IgG range. Conventional infusion of IVIG can reduce or normalize serum IgM levels, return to normal growth, and disappear clinical symptoms; some patients with neutropenia are relieved.
Sulfoxazole/trimethoprim (complex sulfamethoxazole) prophylactic treatment to prevent Pneumocystis carinii pneumonia. Persistent neutropenia can be treated with filgrastim (G-CSF). Complicated with lymphocytosis, arthritis or other autoimmune diseases, hormone therapy can be used in children who do not respond to IVIG.
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