Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Ethical Consideration
2.3. Subjects
- (1)
- Sample information: unique identifier of the study participant and type of drug therapy;
- (2)
- Information about the anthropometric characteristics of the participant: gender, height, weight, body mass index, age at the time of the examination;
- (3)
- Information about the clinical and medical characteristics of the participant: diagnosis or code ICD-10, Steinbroker stage, concomitant diseases, history of therapy of the underlying disease, drug prescribed in the study, duration of the disease (months), assessment of disease activity by DAS28-ESR indices, assessment of disease activity by CDAI indices, assessment of functional status by HAQ index;
- (4)
- Information on clinical biochemical parameters of blood: the level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), CCP (cyclic citrullinated peptide) antibodies.
2.4. Preanalytical Stage for Proteomic Analysis
2.5. Proteomic Analysis
2.6. Preanalytical Stage for Metabolomic Analysis
2.7. Metabolic Analysis
2.8. Data Analysis
3. Results
3.1. Proteome Analysis
3.2. Metabolome Analysis
3.3. Human IL-6 and TNF Immunoassay
3.4. Association of Antibodies with anti-TNF and anti-IL6 Therapies
4. Discussion
4.1. Relation of anti-TNF and anti-IL6 Therapy to the Multiple Autoantibodies Inreconnection
4.2. Does anti-TNF and anti-IL6 Therapy Have Even Chances to Cope with the Disease?
4.3. Essential Condition for the Successful Therapy
4.4. Rebellion of Arginine
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameter | Treatment Strategy | ||
---|---|---|---|
TNFi | IL6i | ||
Sample size (n) | 24 | 16 | |
Disease duration, months | 130.5 ± 129.4 | 157 ± 150 | |
Anthropometric information | Male, % | 21 | 27 |
Age, means, years | 54.0 ± 11.1 | 55.5 ± 11.8 | |
Height ± SD, cm | 167.5 ± 7.4 | 167 ± 7.2 | |
Weight ± SD, kg | 70.86 ± 13.87 | 70.3 ± 14.3 | |
Smokers, % | - | 37 | |
Clinical Information | Diagnosis: M05.8, % | 86 | 64 |
Diagnosis: M05.3, % | 14 | 36 | |
CCP antibodies, positive, % | 50 | 100 | |
Adalimumab, % | 42 | - | |
Etanercept, % | 29 | - | |
Dalibra, % | 29 | - | |
Upadacitinib, % | - | - | |
Sarilumab, % | - | 100 | |
Assessment of disease activity | Steinbroker | 2.5 ± 0.8 | 2.6 ± 0.7 |
CDAI ± SD | 27.8 ± 9.3 | 29.4 ± 10.1 | |
DAS-28 ± SD | 5.35 ± 0.95 | 5.4 ± 1.1 | |
HAQ ± SD | 0.35 ± 0.44 | 0.06 ± 0.19 | |
Biochemistry of blood | CRP, mg/mL | 21.4 ± 26 | 22.4 ± 28.2 |
ESR, mm/h | 26.6 ± 15 | 23.6 ± 14.3 |
UniProt ID | Protein Name | Freq | FC | LOG FC | Biological Process |
---|---|---|---|---|---|
anti-αTNF | |||||
P01871 | Ig heavy constant mu | 1 | 19.11 | 4.26 | Adaptive immunity |
A0M8Q6 | Ig lambda constant 7 | 1 | 11.03 | 3.46 | |
P01877 | Ig heavy constant alpha 2 | 1 | 7.84 | 2.97 | |
P0CG04 | Ig lambda constant 1 | 1 | 7.82 | 2.97 | |
P01876 | Ig heavy constant alpha 1 | 1 | 7.78 | 2.96 | |
B9A064 | Ig lambda-like polypeptide 5 | 1 | 7.35 | 2.88 | |
P0DOY2 | Ig lambda constant 2 | 1 | 6.81 | 2.77 | |
P0DOY3 | Ig lambda constant 3 | 1 | 6.81 | 2.77 | |
P01860 | Ig heavy constant gamma 3 | 1 | 5.97 | 2.58 | |
P0CF74 | Ig lambda constant 6 | 1 | 5.73 | 2.52 | |
P01861 | Ig heavy constant gamma 4 | 1 | 5.54 | 2.47 | |
P19652 | Alpha-1-acid glycoprotein 2 | 1 | 5.38 | 2.43 | Acute phase |
P01023 | Alpha-2-macroglobulin | 1 | 5.13 | 2.36 | |
P01024 | Complement C3 | 1 | 4.94 | 2.31 | Complement alternate pathway |
P01009 | Alpha-1-antitrypsin | 1 | 4.92 | 2.30 | Acute phase |
P01857 | Ig heavy constant gamma 1 | 1 | 4.43 | 2.15 | Adaptive immunity |
P02790 | Hemopexin | 1 | 4.20 | 2.07 | Transport |
P02765 | Alpha-2-HS-glycoprotein | 1 | 4.17 | 2.06 | Mineral balance |
P00739 | Haptoglobin-related protein | 0.8 | 0.25 | −2.01 | Acute inflammatory response |
anti-IL6 | |||||
P01009 | Alpha-1-antitrypsin | 1 | 0.34 | −1.37 | Acute phase |
P01023 | Alpha-2-macroglobulin | 0.87 | 2.2 | 1.1 | |
P01024 | Complement C3 | 0.57 | 2.7 | 1.4 | Complement alternate pathway |
P02765 | Alpha-2-HS-glycoprotein | 0.57 | 3.4 | 1.8 | Mineral balance |
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Stepanov, A.A.; Malsagova, K.A.; Kopylov, A.T.; Rudnev, V.R.; Karateev, D.E.; Markelova, E.I.; Luchikhina, E.L.; Borisova, E.E.; Kaysheva, A.L. Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis. Life 2023, 13, 596. https://doi.org/10.3390/life13020596
Stepanov AA, Malsagova KA, Kopylov AT, Rudnev VR, Karateev DE, Markelova EI, Luchikhina EL, Borisova EE, Kaysheva AL. Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis. Life. 2023; 13(2):596. https://doi.org/10.3390/life13020596
Chicago/Turabian StyleStepanov, Alexander A., Kristina A. Malsagova, Arthur T. Kopylov, Vladimir R. Rudnev, Dmitry E. Karateev, Evgenia I. Markelova, Elena L. Luchikhina, Elena E. Borisova, and Anna L. Kaysheva. 2023. "Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis" Life 13, no. 2: 596. https://doi.org/10.3390/life13020596