What are the genetic changes related to granulomatosis with polyangiitis ?
The genetic basis of GPA is not well understood. Having a particular version of the HLA-DPB1 gene is the strongest genetic risk factor for developing this condition, although several other genes, some of which have not been identified, may be involved. It is likely that a combination of genetic and environmental factors lead to GPA.  GPA is an autoimmune disorder. Such disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Approximately 90 percent of people with GPA have an abnormal immune protein called an anti-neutrophil cytoplasmic antibody (ANCA) in their blood. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but ANCAs attack normal human proteins. Most people with GPA have an ANCA that attacks the human protein proteinase 3 (PR3). A few affected individuals have an ANCA that attacks a protein called myeloperoxidase (MPO). When these antibodies attach to the protein they recognize, they trigger inflammation, which contributes to the signs and symptoms of GPA.  The HLA-DPB1 gene belongs to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A particular variant of the HLA-DPB1 gene called HLA-DPB1*0401 has been found more frequently in people with GPA, especially those with ANCAs, than in people without the condition.  Because the HLA-DPB1 gene is involved in the immune system, changes in it might be related to the autoimmune response and inflammation in the respiratory tract and kidneys characteristic of GPA. However, it is unclear what specific role the HLA-DPB1*0401 gene variant plays in development of this condition.