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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 ILDIndex as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the ILDIndex. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (ILDIndex = 0.652, with specificity and sensitivity of 0.882 and 1.000, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the ILDIndex as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for ILDIndex is 0.960.
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f3-bmi-10-2015-063: Evaluation of ILDIndex as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the ILDIndex. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (ILDIndex = 0.652, with specificity and sensitivity of 0.882 and 1.000, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the ILDIndex as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for ILDIndex is 0.960.

Mentions: ILDIndex was generated from KL-6 values and MICA/Class I ratios and evaluated as a marker for ILD in RA; ILDIndex = exp[4.28 × 10−4 × (KL-6) + 0.576 × (MICA/Class I)]/[1 + exp{4.28 × 10−4 × (KL-6) + 0.576 × (MICA/Class I)}]. ILDIndex was markedly higher in the ILD(+)RA group [Figure 3A, P = 6.71 × 10−6, mean ± SD = 0.714 ± 0.089 in ILD(+)RA, 0.586 ± 0.047 in ILD(−)RA]. The AUC value of the ROC curve for the ILDIndex was 0.960 (Fig. 3B). Specificities and sensitivities of ILDIndex were estimated from the ROC curve conditional on the highest Youden’s index. The optimized cut-off level was 0.652 for ILD in RA with relatively high sensitivity (1.000) and specificity (0.882).


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 ILDIndex as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the ILDIndex. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (ILDIndex = 0.652, with specificity and sensitivity of 0.882 and 1.000, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the ILDIndex as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for ILDIndex is 0.960.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-bmi-10-2015-063: Evaluation of ILDIndex as a marker for interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. (A) Distribution of the ILDIndex. Horizontal bars denote the means. The horizontal dotted line represents an optimized cut-off level (ILDIndex = 0.652, with specificity and sensitivity of 0.882 and 1.000, respectively). ILD(+)RA: RA with ILD, ILD(−)RA: RA without ILD. (b) The receiver operating characteristic (ROC) curve using the ILDIndex as markers for ILD in RA. The area under the curve (AUC) value of the ROC curve for ILDIndex is 0.960.
Mentions: ILDIndex was generated from KL-6 values and MICA/Class I ratios and evaluated as a marker for ILD in RA; ILDIndex = exp[4.28 × 10−4 × (KL-6) + 0.576 × (MICA/Class I)]/[1 + exp{4.28 × 10−4 × (KL-6) + 0.576 × (MICA/Class I)}]. ILDIndex was markedly higher in the ILD(+)RA group [Figure 3A, P = 6.71 × 10−6, mean ± SD = 0.714 ± 0.089 in ILD(+)RA, 0.586 ± 0.047 in ILD(−)RA]. The AUC value of the ROC curve for the ILDIndex was 0.960 (Fig. 3B). Specificities and sensitivities of ILDIndex were estimated from the ROC curve conditional on the highest Youden’s index. The optimized cut-off level was 0.652 for ILD in RA with relatively high sensitivity (1.000) and specificity (0.882).

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