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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

Evaluation of the ratio of the average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels to the average anti-human leukocyte antigen (HLA) class I Ab levels (MICA/Class I), as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the MICA/Class I ratio. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (MICA/Class I = 0.770, with specificity and sensitivity of 0.882 and 0.824, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the MICA/Class I ratio (solid line) and KL-6 (dotted line) as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for MICA/Class I is 0.912 and that for KL-6 is 0.853. (C) Distribution of KL-6. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (KL-6 = 296, with specificity and sensitivity of 0.824 and 0.875, respectively).
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f2-bmi-10-2015-063: Evaluation of the ratio of the average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels to the average anti-human leukocyte antigen (HLA) class I Ab levels (MICA/Class I), as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the MICA/Class I ratio. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (MICA/Class I = 0.770, with specificity and sensitivity of 0.882 and 0.824, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the MICA/Class I ratio (solid line) and KL-6 (dotted line) as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for MICA/Class I is 0.912 and that for KL-6 is 0.853. (C) Distribution of KL-6. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (KL-6 = 296, with specificity and sensitivity of 0.824 and 0.875, respectively).

Mentions: Anti-HLA class I and class II Ab levels in ILD(+)RA tended to be lower than in the ILD(−)RA group, but these differences did not reach statistical significance. However, anti-MICA Ab levels were significantly elevated in the ILD(+)RA group. Mean Ab levels were calculated so that they reflected the levels of auto-Abs for common domains of HLA molecules by reducing the effects of allele-specific allo-Abs. The averages of anti-HLA class I and class II Ab levels in ILD(+)RA tended to be lower than in the ILD(−)RA group. In contrast, the average of anti-MICA Ab levels was significantly higher in the ILD(+)RA group. The ratio of the average anti-MICA Ab levels to the average anti-HLA class I Ab levels (MICA/Class I) was markedly higher in the ILD(+)RA group (Table 2, Fig. 2A). The sample size estimated on this analysis with the power of 80% to detect association is 50 each. Similarly, the ratio of anti-MICA Ab levels to anti-HLA class II Ab levels and of anti-MICA Ab levels to anti-HLA Ab levels were also higher in the ILD(+)RA group. Thus, anti-MICA Ab levels in the ILD(+)RA group are higher than in the ILD(−)RA group.


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)

Evaluation of the ratio of the average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels to the average anti-human leukocyte antigen (HLA) class I Ab levels (MICA/Class I), as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the MICA/Class I ratio. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (MICA/Class I = 0.770, with specificity and sensitivity of 0.882 and 0.824, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the MICA/Class I ratio (solid line) and KL-6 (dotted line) as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for MICA/Class I is 0.912 and that for KL-6 is 0.853. (C) Distribution of KL-6. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (KL-6 = 296, with specificity and sensitivity of 0.824 and 0.875, respectively).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4539100&req=5

f2-bmi-10-2015-063: Evaluation of the ratio of the average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels to the average anti-human leukocyte antigen (HLA) class I Ab levels (MICA/Class I), as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the MICA/Class I ratio. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (MICA/Class I = 0.770, with specificity and sensitivity of 0.882 and 0.824, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the MICA/Class I ratio (solid line) and KL-6 (dotted line) as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for MICA/Class I is 0.912 and that for KL-6 is 0.853. (C) Distribution of KL-6. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (KL-6 = 296, with specificity and sensitivity of 0.824 and 0.875, respectively).
Mentions: Anti-HLA class I and class II Ab levels in ILD(+)RA tended to be lower than in the ILD(−)RA group, but these differences did not reach statistical significance. However, anti-MICA Ab levels were significantly elevated in the ILD(+)RA group. Mean Ab levels were calculated so that they reflected the levels of auto-Abs for common domains of HLA molecules by reducing the effects of allele-specific allo-Abs. The averages of anti-HLA class I and class II Ab levels in ILD(+)RA tended to be lower than in the ILD(−)RA group. In contrast, the average of anti-MICA Ab levels was significantly higher in the ILD(+)RA group. The ratio of the average anti-MICA Ab levels to the average anti-HLA class I Ab levels (MICA/Class I) was markedly higher in the ILD(+)RA group (Table 2, Fig. 2A). The sample size estimated on this analysis with the power of 80% to detect association is 50 each. Similarly, the ratio of anti-MICA Ab levels to anti-HLA class II Ab levels and of anti-MICA Ab levels to anti-HLA Ab levels were also higher in the ILD(+)RA group. Thus, anti-MICA Ab levels in the ILD(+)RA group are higher than in the ILD(−)RA group.

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