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Autoantibody Profiles in Collagen Disease Patients with Interstitial Lung Disease (ILD): Antibodies to Major Histocompatibility Complex Class I-Related Chain A (MICA) as Markers of ILD.

Furukawa H, Oka S, Shimada K, Masuo K, Nakajima F, Funano S, Tanaka Y, Komiya A, Fukui N, Sawasaki T, Tadokoro K, Nose M, Tsuchiya N, Tohma S - Biomark Insights (2015)

Bottom Line: It is then designated as collagen vascular disease-associated ILD (CVD-ILD), and influences patients' prognosis.The ratio of the average anti-MICA Ab level to the average anti-human leukocyte antigen class I Ab level (ie, MICA/Class I) was significantly higher in RA patients with CVD-ILD compared with those without (P = 4.47 × 10(-5)).The MICA/Class I ratio could be a better marker for diagnosing CVD-ILD than KL-6 (Krebs von den lungen-6).

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan. ; Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

ABSTRACT
Interstitial lung disease (ILD) is frequently associated with collagen disease. It is then designated as collagen vascular disease-associated ILD (CVD-ILD), and influences patients' prognosis. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in patients with collagen disease is quite poor. Here, we report our investigation of auto-antibody (Ab) profiles to determine whether they may be useful in diagnosing CVD-ILD or AoDILD in collagen disease. Auto-Ab profiles were analyzed using the Lambda Array Beads Multi-Analyte System, granulocyte immunofluorescence test, Proto-Array Human Protein Microarray, AlphaScreen assay, and glutathione S-transferase capture enzyme-linked immunosorbent assay in 34 patients with rheumatoid arthritis (RA) with or without CVD-ILD and in 15 patients with collagen disease with AoDILD. The average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels were higher in RA patients with CVD-ILD than in those without (P = 0.0013). The ratio of the average anti-MICA Ab level to the average anti-human leukocyte antigen class I Ab level (ie, MICA/Class I) was significantly higher in RA patients with CVD-ILD compared with those without (P = 4.47 × 10(-5)). To the best of our knowledge, this is the first report of auto-Ab profiles in CVD-ILD. The MICA/Class I ratio could be a better marker for diagnosing CVD-ILD than KL-6 (Krebs von den lungen-6).

No MeSH data available.


Related in: MedlinePlus

Hypotheses on the roles of anti-MICA Abs. (A) Anti-MICA Abs block the NKG2D–MICA interaction and prevent the stimulation of CD8+ T cells or NK cells for clearance of microorganisms, causing sustained inflammation followed by the fibrotic changes of the lung. (b) Chronically produced auto-Abs for MICA in RA patients may cause injury of the pulmonary epithelial cells expressing MICA by antibody-dependent cellular cytotoxicity.
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f5-bmi-10-2015-063: Hypotheses on the roles of anti-MICA Abs. (A) Anti-MICA Abs block the NKG2D–MICA interaction and prevent the stimulation of CD8+ T cells or NK cells for clearance of microorganisms, causing sustained inflammation followed by the fibrotic changes of the lung. (b) Chronically produced auto-Abs for MICA in RA patients may cause injury of the pulmonary epithelial cells expressing MICA by antibody-dependent cellular cytotoxicity.

Mentions: MICA is a non-classical HLA class I antigen encoded in the HLA region of chromosome 6 and is highly polymorphic. MICA is a ligand of NKG2D, one of the natural killer (NK) receptors expressed on T cells and NK cells.35,36 Pulmonary epithelial cells infected with Pseudomonas aeruginosa upregulate cell-surface expression of ligands of NKG2D, which play important roles in the clearance of the bacteria.37,38Escherichia coli and Mycobacterium tuberculosis infection also increase cell-surface expression of NKG2D ligands.39,40 Anti-MICA Abs in patients with collagen disease may block the NKG2D–MICA interaction and prevent the stimulation of T cells or NK cells for clearance of bacteria, causing sustained inflammation followed by the fibrotic changes of the lung (Fig. 5).


Autoantibody Profiles in Collagen Disease Patients with Interstitial Lung Disease (ILD): Antibodies to Major Histocompatibility Complex Class I-Related Chain A (MICA) as Markers of ILD.

Furukawa H, Oka S, Shimada K, Masuo K, Nakajima F, Funano S, Tanaka Y, Komiya A, Fukui N, Sawasaki T, Tadokoro K, Nose M, Tsuchiya N, Tohma S - Biomark Insights (2015)

Hypotheses on the roles of anti-MICA Abs. (A) Anti-MICA Abs block the NKG2D–MICA interaction and prevent the stimulation of CD8+ T cells or NK cells for clearance of microorganisms, causing sustained inflammation followed by the fibrotic changes of the lung. (b) Chronically produced auto-Abs for MICA in RA patients may cause injury of the pulmonary epithelial cells expressing MICA by antibody-dependent cellular cytotoxicity.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539100&req=5

f5-bmi-10-2015-063: Hypotheses on the roles of anti-MICA Abs. (A) Anti-MICA Abs block the NKG2D–MICA interaction and prevent the stimulation of CD8+ T cells or NK cells for clearance of microorganisms, causing sustained inflammation followed by the fibrotic changes of the lung. (b) Chronically produced auto-Abs for MICA in RA patients may cause injury of the pulmonary epithelial cells expressing MICA by antibody-dependent cellular cytotoxicity.
Mentions: MICA is a non-classical HLA class I antigen encoded in the HLA region of chromosome 6 and is highly polymorphic. MICA is a ligand of NKG2D, one of the natural killer (NK) receptors expressed on T cells and NK cells.35,36 Pulmonary epithelial cells infected with Pseudomonas aeruginosa upregulate cell-surface expression of ligands of NKG2D, which play important roles in the clearance of the bacteria.37,38Escherichia coli and Mycobacterium tuberculosis infection also increase cell-surface expression of NKG2D ligands.39,40 Anti-MICA Abs in patients with collagen disease may block the NKG2D–MICA interaction and prevent the stimulation of T cells or NK cells for clearance of bacteria, causing sustained inflammation followed by the fibrotic changes of the lung (Fig. 5).

Bottom Line: It is then designated as collagen vascular disease-associated ILD (CVD-ILD), and influences patients' prognosis.The ratio of the average anti-MICA Ab level to the average anti-human leukocyte antigen class I Ab level (ie, MICA/Class I) was significantly higher in RA patients with CVD-ILD compared with those without (P = 4.47 × 10(-5)).The MICA/Class I ratio could be a better marker for diagnosing CVD-ILD than KL-6 (Krebs von den lungen-6).

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan. ; Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

ABSTRACT
Interstitial lung disease (ILD) is frequently associated with collagen disease. It is then designated as collagen vascular disease-associated ILD (CVD-ILD), and influences patients' prognosis. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in patients with collagen disease is quite poor. Here, we report our investigation of auto-antibody (Ab) profiles to determine whether they may be useful in diagnosing CVD-ILD or AoDILD in collagen disease. Auto-Ab profiles were analyzed using the Lambda Array Beads Multi-Analyte System, granulocyte immunofluorescence test, Proto-Array Human Protein Microarray, AlphaScreen assay, and glutathione S-transferase capture enzyme-linked immunosorbent assay in 34 patients with rheumatoid arthritis (RA) with or without CVD-ILD and in 15 patients with collagen disease with AoDILD. The average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels were higher in RA patients with CVD-ILD than in those without (P = 0.0013). The ratio of the average anti-MICA Ab level to the average anti-human leukocyte antigen class I Ab level (ie, MICA/Class I) was significantly higher in RA patients with CVD-ILD compared with those without (P = 4.47 × 10(-5)). To the best of our knowledge, this is the first report of auto-Ab profiles in CVD-ILD. The MICA/Class I ratio could be a better marker for diagnosing CVD-ILD than KL-6 (Krebs von den lungen-6).

No MeSH data available.


Related in: MedlinePlus