Diffuse panbronchiolitis pathophysiology
|
Diffuse panbronchiolitis Microchapters |
|
Differentiating Diffuse panbronchiolitis from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Diffuse panbronchiolitis pathophysiology On the Web |
|
American Roentgen Ray Society Images of Diffuse panbronchiolitis pathophysiology |
|
Risk calculators and risk factors for Diffuse panbronchiolitis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
DPB remains idiopathic, which means an exact physiological, environmental, or pathogenic cause of the disease is unknown.[1] However, several known factors are involved with the pathogenesis of DPB.[2][3]
The major histocompatibility complex (MHC) is a large genomic region found in most vertebrates, that is associated with mating and the immune system. It is located on chromosome 6 in humans. A subset of the human MHC is human leukocyte antigen (HLA), which controls the antigen presenting system, as part of adaptive immunity against pathogens such as bacteria and viruses.
Genetic predisposition for DPB has been localized to two HLA haplotypes unique to Asians, particularly of East Asian descent.[2][4] HLA-B54 is associated with DPB in Japanese patients,[2] while HLA-A11 is associated with the disease in Koreans.[3] One or more candidate genes[5] (a gene suspected to be responsible for a trait or disease) within this region of class I HLA are believed to be the genetic factor responsible for DPB, allowing disease susceptibility[4] related to the structure of the antigen presenting molecules selected by these genes.[6]
Candidate genes within HLA that are most likely involved with DPB suceptibility include: C6orf37[5] and TAP2.[6]
Another such gene, though not a part of the HLA system, is the gene for interleukin 8 (IL-8)[7] located on chromosome 4. The role of IL-8 to produce inflammation by causing the proliferation of neutrophil granulocytes at any site of pathogenic involvement, in conjunction with strong microsatellite identification with DPB, implicates IL-8 as another candidate gene associated with DPB pathogenesis.[7] This also supports the idea that several factors, including those unrelated to HLA as well as non-genetic, and unknown factors, may cause the disease.[7]
The inflammation common to DPB also provides a means to determine other mechanisms of disease pathogenesis.[8] This may be partly due to the persistence of inflammation in DPB, with or without the presence of the two opportunistic bacteria sometimes found with the disease (haemophilus influenzae, pseudomonas aeruginosa).[9] Inflammation caused by the chemokine MIP-1alpha and its involvement with CD8+ T-cells is believed to be one such mechanism of DPB pathogenesis.[8]
Other factors found with DPB play a part in its pathogenesis by sometimes causing minor variations of it.
Beta defensins, a family of antimicrobial peptides found in the respiratory tract, are responsible for further inflammation in DPB, when associated pathogens like pseudomonas aerugenosa are present.[10]
If present in a DPB patient, the human T-lymphotropic virus, type I, a retrovirus, modifies DPB pathogenesis by infecting CD4+ cells (Helper T-cells) and altering there effectiveness in reducing both known and unknown pathogenic involvement with DPB.[11] Conversely, an onset of DPB causes increased frequency of Adult T-cell leukemia in human lymphotropic virus sufferers.[11]
References
- ↑ Poletti V, Casoni G, Chilosi M, Zompatori M (2006). "Diffuse panbronchiolitis". Eur Respir J. 28 (4): 862–871. PMID 17012632.
- ↑ 2.0 2.1 2.2 Keicho N, Tokunaga K, Nakata K, Taguchi Y, Azuma A, Bannai M, Emi M, Ohishi N, Yazaki Y, Kudoh S (1998). "Contribution of HLA genes in genetic predisposition for diffuse panbronchiolitis". Am J Respir Crit Care Med. 158 (3): 846–850. PMID 9731015.
- ↑ 3.0 3.1 Park MH, Kim YW, Yoon HI, Yoo CD, Han SK, Shim YS, Kim WD (1999). "Association of HLA class I antigens with diffuse panbronchiolitis in Korean patients". Am J Respir Crit Care Med. 159 (2): 526–529. PMID 9927368.
- ↑ 4.0 4.1 Keicho N, Ohashi J, Tamiya G, Nakata K, Taguchi Y, Azuma A, Ohishi N, Emi M, Park MH, Inoko H, Tokunaga K, Kudoh S (2000). "Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis". Am J Hum Genet. 66 (2): 501–507. PMID 10677310.
- ↑ 5.0 5.1 Matsuzaka Y, Tounai K, Denda A, Tomizawa M, Makino S, Okamoto K, Keicho N, Oka A, Kulski JK, Tamiya G, Inoko H (2002). "Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC". Immunogenetics. 54 (5): 301–309. PMID 12185533.
- ↑ 6.0 6.1 Keicho N, Tokunaga K, Nakata K, Taguchi Y, Azuma A, Tanabe K, Matsushita M, Emi M, Ohishi N, Kudoh S (1999). "Contribution of TAP genes to genetic predisposition for diffuse panbronchiolitis". Tissue Antigens. 53 (4 pt. 1): 366–373. PMID 10323341.
- ↑ 7.0 7.1 7.2 Emi M, Keicho N, Tokunaga K, Katsumata H, Souma S, Nakata K, Taguchi Y, Ohishi N, Azuma A, Kudoh S (1999). "Association of diffuse panbronchiolitis with microsatellite polymorphisms of the human interleukin 8 (IL-8) gene". J Hum Genet. 44 (3): 169–172. PMID 10319580.
- ↑ 8.0 8.1 Kadota J, Mukae H, Tomono K, Kohno S (2001). "High concentrations of beta-chemokines in BAL fluid of patients with diffuse panbronchiolitis". Chest. 120 (2): 602–607. PMID 11502665.
- ↑ Yanagihara K, Kadoto J, Kohno S (2001). "Diffuse panbronchiolitis--pathophysiology and treatment mechanisms". Int J Antimicrob Agents. 18 (Suppl. 1): S83–87. PMID 11574201.
- ↑ Hiratsuka T, Mukae H, Iiboshi H, Ashitani J, Nabeshima K, Minematsu T, Chino N, Ihi T, Kohno S, Nakazato M (2003). "Increased concentrations of human beta-defensins in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis". Thorax. 58 (5): 425–430. PMID 12728165.
- ↑ 11.0 11.1 Yamamoto M, Matsuyama W, Oonakahara K, Watanabe M, Higashimoto I, Kawabata M, Osame M, Arimura K (2004). "Influence of human T lymphotropic virus type I on diffuse pan-bronchiolitis". Clin Exp Immunol. 136 (3): 513–520. PMID 15147354.