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*For medical professionals to read only, the era when ANCA dominates AAV markers has changed~2021 Asia-Pacific Rheumatism Alliance (APLAR) Annual Meeting will be held in Kyoto, Japan on August 28~31, 2021, Professor Jun Ishizaki, Ehime University, Japan On August 31st, I shared the new biomarkers of ANCA-related vasculitis disease activity.
Come and learn about it~ Figure 1 Professor Jun Ishizaki's speech topic ANCA-related vasculitis, relieving recurrence is like a neutrophil cell Antibody (ANCA)-associated vasculitis (AAV) includes 3 different diseases: granulomatous polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatous polyangiitis (EGPA)
.
It is a group of inflammatory diseases that mainly involves small blood vessels throughout the body.
It is characterized by the production of autoantibodies against protease 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) in the cytoplasm of neutrophils [1]
.
For AAV, relapse after remission is common in clinical [2]
.
ANCA was proposed as a marker of disease recurrence as early as its introduction as a clinical test [3]
.
In a prospective Japanese cohort study, the increase of MPO-ANCA was significantly associated with subsequent recurrence, while the persistence of MPO-ANCA was not related to the recurrence rate [4]
.
Figure 2 The limitations of ANCA as a marker of disease remission and recurrence, but so far, the test indicators for AAV recurrence are still an unsolved mystery.
ANCA and traditional acute phase indicators, such as C-reactive protein (CRP), are used in clinical practice As a biomarker of disease activity and predictor of recurrence
.
However, these biomarkers have low sensitivity and specificity for monitoring disease activity
.
At present, some biomarkers have been reported in the literature for monitoring disease activity or predicting recurrence; however, none of them have been used in clinical practice [5]
.
AAV marker, TIMP-1, is used to predict Professor Jun Ishizaki's discovery that there is currently a lack of factors predicting the continued remission of AAV, so he began to explore it
.
They obtained serum samples from a large Japanese cohort study and used targeted proteomics to identify promising biomarkers related to AAV disease activity, disease severity, and organ involvement [6]
.
The levels of such candidates in matched AAV serum samples before treatment (active period) and 6 months after treatment (remission period) and samples of healthy control subjects were analyzed by ELISA, and the levels of these 8 markers in active period were found The serum level was significantly higher than the remission period
.
Figure 3 Marker levels of highly active ANCA-AAV remission before treatment and 6 months after treatment.
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is the best-performing disease activity marker and can be used at the beginning of remission induction therapy 6 Separate lightly or highly active AAV from alleviating AAV after one month
.
Studies have screened 28 markers related to inflammation, angiogenesis, tissue damage and repair, and also show that TIMP-1 has the potential to monitor disease activity
.
Therefore, Professor Jun Ishizaki conducted a detailed analysis of the TIMP-1 level in the clinical process of AAV patients to verify whether TIMP-1 can be used as a clinical predictor of relapse and sustained remission during maintenance treatment
.
Figure 4 TIMP-1 potential to monitor disease activity TIMP-1 <150ng/ml, AAV long-term maintenance remission Professor Jun Ishizaki collected follow-up data at 3, 6, 12 and 18 months of treatment and at the time of relapse, including clinical manifestations and experiments Laboratory data, etc.
, analyzed the patient’s serum before the start of treatment and 6 months after treatment.
The results showed that after 6 months of treatment, the TIMP-1 level in the serum of remission patients was significantly lower than that of non-remission patients, and the performance was better than that of non-remission patients.
CRP and MPO-ANCA
.
Figure 5 TIMP-1 is a superior biomarker of ANCA-AAV.
They also found that the serum TIMP-1 level of relapsed patients increased (191–205 ng/ml) 6 months before the relapse, which was earlier than the increase of serum CRP level.
High; most patients with TIMP-1 levels <150ng/ml maintain remission for at least 12 months
.
TIMP-1 level is more useful as a predictive biomarker of sustained remission of AAV than as a predictor of recurrence of maintenance treatment.
TIMP-1 level <150 ng/ml is an important indicator for predicting long-term maintenance of remission [5]
.
Summary: 1.
The management of AAV patients by monitoring ANCA is limited, and it is very important to explore other markers of disease activity
.
2.
During remission induction and maintenance remission treatment, TIMP-1 level is better than CRP and MPO-ANCA related biomarkers of disease activity
.
3.
TIMP-1 level is more useful as a biomarker for predicting sustained remission than predicting relapse in AAV maintenance remission treatment
.
4.
TIMP-1 level <150ng/ml suggests that AAV can maintain remission for a long time
.
Experts comment that AAV is a type of systemic vasculitis characterized by pulmonary and renal vasculitis.
The clinical application of glucocorticoid combined with cyclophosphamide has significantly improved the prognosis of patients, but the recurrence rate of the disease is as high as 70% to 90 %, so regular follow-up and condition assessment of AAV patients are the key and difficult points of long-term management
.
When assessing disease activity, the Birmingham Vasculitis Activity Score (BVAS) is the most accurate for a comprehensive assessment of the disease.
However, due to the limitations of physician experience and examination costs, not every assessment can complete all the items involved in BVAS, including lungs.
section CT, sinus CT, EMG and nerve conduction audiometry the like
.
Therefore, clinicians always hope to find some serological indicators related to disease activity, assist in assessing the patient's disease activity, and predict long-term prognosis and recurrence
.
As an important factor in the pathogenesis of AAV, the wide application of ANCA in the diagnosis of AAV disease has been recognized, but in the long-term management of the disease, it has been found that the titer of ANCA has a low correlation with disease activity, sustained remission and recurrence
.
Prof.
Ishizaki and others analyzed the biomarkers in the serum of 69 AAV patients who were followed up for more than 18 months, combined with the BVAS assessment results of the patients, and found that TIMP-1 is superior to CRP and MPO-ANCA.
Both sustained remission and relapse have certain sensitivity and specificity
.
Due to the low positive rate of PR3-ANCA, no significant analysis results were obtained in this study
.
Although the sample size of the study is not large, the results of a prospective longitudinal study have certain significance for guiding clinical practice: patients with a continuous TIMP-1 level of <150ng/ml can consider gradual reduction of hormones, but still need more The sample cohort undergoes long-term verification
.
Expert profile Li Jing, Associate Professor, Department of Rheumatology and Immunology, Peking Union Medical College Hospital, Deputy Chief Physician, Associate Professor, Master's Tutor, Young Member of the Rheumatology and Immunology Physician Branch of the Chinese Medical Doctor Association, Member of the Vasculitis Group, Secretary, Cross-Strait Medicine and Health Exchange Association Rheumatology and Immunology Expert Committee Vascular Member and Secretary of the Inflammation Group Project: presided over the National Natural Science Foundation of China, participated in the "13th Five-Year Plan" project of the Ministry of Science and Technology, etc.
Articles: published more than 30 articles in Chinese core journals and SCI magazines, and published SCI as the first author and corresponding author Article 15 editorial board members: "Chinese Journal of Clinical Immunity and Allergy", and reviewing manuscripts for many domestic core and foreign SCI journals.
Research direction: systemic vasculitis, rheumatoid arthritis References: [1] Kitching AR, Anders HJ,Basu N,et al.
ANCA-associated vasculitis.
Nat Rev Dis Primers.
2020;6(1):71.
Published 2020 Aug 27.
doi:10.
1038/s41572-020-0204-y[2]Salama AD.
Relapse in Anti-Neutrophil Cytoplasm Antibody(ANCA)-Associated Vasculitis.
Kidney Int Rep.
2019;5(1):7-12.
Published 2019 Oct 24.
doi:10.
1016/j.
ekir.
2019.
10.
005[3]Tervaert JW, Huitema MG,HenéRJ,et al.
Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre.
Lancet.
1990;336(8717):709-711.
doi:10.
1016/0140-6736(90)92205-v[ 4] Watanabe H, Sada KE, Matsumoto Y, et al.
Association Between Reappearance of Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis:Subgroup Analysis of Nationwide Prospective Cohort Studies.
Arthritis Rheumatol.
2018;70(10):1626-1633.
doi:10.
1002/art.
40538[5 ]Ishizaki J, Takemori A, Horie K, et al.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471-5[6]Ishizaki J,Takemori A,Suemori K,et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-3Subgroup Analysis of Nationwide Prospective Cohort Studies.
Arthritis Rheumatol.
2018;70(10):1626-1633.
doi:10.
1002/art.
40538[5]Ishizaki J,Takemori A,Horie K,et al.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471-5[6]Ishizaki J, Takemori A, Suemori K, et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi: 10.
1186/s13075-017-1429-3Subgroup Analysis of Nationwide Prospective Cohort Studies.
Arthritis Rheumatol.
2018;70(10):1626-1633.
doi:10.
1002/art.
40538[5]Ishizaki J,Takemori A,Horie K,et al.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471-5[6]Ishizaki J, Takemori A, Suemori K, et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi: 10.
1186/s13075-017-1429-3Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471 -5[6]Ishizaki J,Takemori A,Suemori K,et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471 -5[6]Ishizaki J,Takemori A,Suemori K,et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3
Come and learn about it~ Figure 1 Professor Jun Ishizaki's speech topic ANCA-related vasculitis, relieving recurrence is like a neutrophil cell Antibody (ANCA)-associated vasculitis (AAV) includes 3 different diseases: granulomatous polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatous polyangiitis (EGPA)
.
It is a group of inflammatory diseases that mainly involves small blood vessels throughout the body.
It is characterized by the production of autoantibodies against protease 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) in the cytoplasm of neutrophils [1]
.
For AAV, relapse after remission is common in clinical [2]
.
ANCA was proposed as a marker of disease recurrence as early as its introduction as a clinical test [3]
.
In a prospective Japanese cohort study, the increase of MPO-ANCA was significantly associated with subsequent recurrence, while the persistence of MPO-ANCA was not related to the recurrence rate [4]
.
Figure 2 The limitations of ANCA as a marker of disease remission and recurrence, but so far, the test indicators for AAV recurrence are still an unsolved mystery.
ANCA and traditional acute phase indicators, such as C-reactive protein (CRP), are used in clinical practice As a biomarker of disease activity and predictor of recurrence
.
However, these biomarkers have low sensitivity and specificity for monitoring disease activity
.
At present, some biomarkers have been reported in the literature for monitoring disease activity or predicting recurrence; however, none of them have been used in clinical practice [5]
.
AAV marker, TIMP-1, is used to predict Professor Jun Ishizaki's discovery that there is currently a lack of factors predicting the continued remission of AAV, so he began to explore it
.
They obtained serum samples from a large Japanese cohort study and used targeted proteomics to identify promising biomarkers related to AAV disease activity, disease severity, and organ involvement [6]
.
The levels of such candidates in matched AAV serum samples before treatment (active period) and 6 months after treatment (remission period) and samples of healthy control subjects were analyzed by ELISA, and the levels of these 8 markers in active period were found The serum level was significantly higher than the remission period
.
Figure 3 Marker levels of highly active ANCA-AAV remission before treatment and 6 months after treatment.
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is the best-performing disease activity marker and can be used at the beginning of remission induction therapy 6 Separate lightly or highly active AAV from alleviating AAV after one month
.
Studies have screened 28 markers related to inflammation, angiogenesis, tissue damage and repair, and also show that TIMP-1 has the potential to monitor disease activity
.
Therefore, Professor Jun Ishizaki conducted a detailed analysis of the TIMP-1 level in the clinical process of AAV patients to verify whether TIMP-1 can be used as a clinical predictor of relapse and sustained remission during maintenance treatment
.
Figure 4 TIMP-1 potential to monitor disease activity TIMP-1 <150ng/ml, AAV long-term maintenance remission Professor Jun Ishizaki collected follow-up data at 3, 6, 12 and 18 months of treatment and at the time of relapse, including clinical manifestations and experiments Laboratory data, etc.
, analyzed the patient’s serum before the start of treatment and 6 months after treatment.
The results showed that after 6 months of treatment, the TIMP-1 level in the serum of remission patients was significantly lower than that of non-remission patients, and the performance was better than that of non-remission patients.
CRP and MPO-ANCA
.
Figure 5 TIMP-1 is a superior biomarker of ANCA-AAV.
They also found that the serum TIMP-1 level of relapsed patients increased (191–205 ng/ml) 6 months before the relapse, which was earlier than the increase of serum CRP level.
High; most patients with TIMP-1 levels <150ng/ml maintain remission for at least 12 months
.
TIMP-1 level is more useful as a predictive biomarker of sustained remission of AAV than as a predictor of recurrence of maintenance treatment.
TIMP-1 level <150 ng/ml is an important indicator for predicting long-term maintenance of remission [5]
.
Summary: 1.
The management of AAV patients by monitoring ANCA is limited, and it is very important to explore other markers of disease activity
.
2.
During remission induction and maintenance remission treatment, TIMP-1 level is better than CRP and MPO-ANCA related biomarkers of disease activity
.
3.
TIMP-1 level is more useful as a biomarker for predicting sustained remission than predicting relapse in AAV maintenance remission treatment
.
4.
TIMP-1 level <150ng/ml suggests that AAV can maintain remission for a long time
.
Experts comment that AAV is a type of systemic vasculitis characterized by pulmonary and renal vasculitis.
The clinical application of glucocorticoid combined with cyclophosphamide has significantly improved the prognosis of patients, but the recurrence rate of the disease is as high as 70% to 90 %, so regular follow-up and condition assessment of AAV patients are the key and difficult points of long-term management
.
When assessing disease activity, the Birmingham Vasculitis Activity Score (BVAS) is the most accurate for a comprehensive assessment of the disease.
However, due to the limitations of physician experience and examination costs, not every assessment can complete all the items involved in BVAS, including lungs.
section CT, sinus CT, EMG and nerve conduction audiometry the like
.
Therefore, clinicians always hope to find some serological indicators related to disease activity, assist in assessing the patient's disease activity, and predict long-term prognosis and recurrence
.
As an important factor in the pathogenesis of AAV, the wide application of ANCA in the diagnosis of AAV disease has been recognized, but in the long-term management of the disease, it has been found that the titer of ANCA has a low correlation with disease activity, sustained remission and recurrence
.
Prof.
Ishizaki and others analyzed the biomarkers in the serum of 69 AAV patients who were followed up for more than 18 months, combined with the BVAS assessment results of the patients, and found that TIMP-1 is superior to CRP and MPO-ANCA.
Both sustained remission and relapse have certain sensitivity and specificity
.
Due to the low positive rate of PR3-ANCA, no significant analysis results were obtained in this study
.
Although the sample size of the study is not large, the results of a prospective longitudinal study have certain significance for guiding clinical practice: patients with a continuous TIMP-1 level of <150ng/ml can consider gradual reduction of hormones, but still need more The sample cohort undergoes long-term verification
.
Expert profile Li Jing, Associate Professor, Department of Rheumatology and Immunology, Peking Union Medical College Hospital, Deputy Chief Physician, Associate Professor, Master's Tutor, Young Member of the Rheumatology and Immunology Physician Branch of the Chinese Medical Doctor Association, Member of the Vasculitis Group, Secretary, Cross-Strait Medicine and Health Exchange Association Rheumatology and Immunology Expert Committee Vascular Member and Secretary of the Inflammation Group Project: presided over the National Natural Science Foundation of China, participated in the "13th Five-Year Plan" project of the Ministry of Science and Technology, etc.
Articles: published more than 30 articles in Chinese core journals and SCI magazines, and published SCI as the first author and corresponding author Article 15 editorial board members: "Chinese Journal of Clinical Immunity and Allergy", and reviewing manuscripts for many domestic core and foreign SCI journals.
Research direction: systemic vasculitis, rheumatoid arthritis References: [1] Kitching AR, Anders HJ,Basu N,et al.
ANCA-associated vasculitis.
Nat Rev Dis Primers.
2020;6(1):71.
Published 2020 Aug 27.
doi:10.
1038/s41572-020-0204-y[2]Salama AD.
Relapse in Anti-Neutrophil Cytoplasm Antibody(ANCA)-Associated Vasculitis.
Kidney Int Rep.
2019;5(1):7-12.
Published 2019 Oct 24.
doi:10.
1016/j.
ekir.
2019.
10.
005[3]Tervaert JW, Huitema MG,HenéRJ,et al.
Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre.
Lancet.
1990;336(8717):709-711.
doi:10.
1016/0140-6736(90)92205-v[ 4] Watanabe H, Sada KE, Matsumoto Y, et al.
Association Between Reappearance of Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis:Subgroup Analysis of Nationwide Prospective Cohort Studies.
Arthritis Rheumatol.
2018;70(10):1626-1633.
doi:10.
1002/art.
40538[5 ]Ishizaki J, Takemori A, Horie K, et al.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471-5[6]Ishizaki J,Takemori A,Suemori K,et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-31186/s13075-017-1429-3Subgroup Analysis of Nationwide Prospective Cohort Studies.
Arthritis Rheumatol.
2018;70(10):1626-1633.
doi:10.
1002/art.
40538[5]Ishizaki J,Takemori A,Horie K,et al.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471-5[6]Ishizaki J, Takemori A, Suemori K, et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi: 10.
1186/s13075-017-1429-3Subgroup Analysis of Nationwide Prospective Cohort Studies.
Arthritis Rheumatol.
2018;70(10):1626-1633.
doi:10.
1002/art.
40538[5]Ishizaki J,Takemori A,Horie K,et al.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471-5[6]Ishizaki J, Takemori A, Suemori K, et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi: 10.
1186/s13075-017-1429-3Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471 -5[6]Ishizaki J,Takemori A,Suemori K,et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2021;23(1):91.
Published 2021 Mar 20.
doi:10.
1186/s13075-021-02471 -5[6]Ishizaki J,Takemori A,Suemori K,et al.
Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Res Ther.
2017;19(1):218.
Published 2017 Sep 29.
doi:10.
1186/s13075-017-1429-3
