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New Biomarker in JIA.pptx

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M
Marwa Besar

- The document analyzes IL-18 and IFN-gamma as biomarkers for diagnosis and prognosis in juvenile idiopathic arthritis (JIA) patients. It finds that IL-18 levels correlate with disease activity and can predict response to therapy, while IFN-gamma levels indicate response to therapy. The study compares biomarker and disease activity measurements in 45 JIA patients at initial presentation and after treatment. It concludes that IL-18 and IFN-gamma may be promising markers for detecting prognosis and treatment response in JIA patients.

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New Biomarker In Diagnosis And Follow Up Juvenile Idiopathic Arthritis patients. (Single Center Experience) Marwa Abou Elmaaty Mohamed Mohamed Besar Lecturer of Internal Medicine (Rheumatology Immunology Unit, Pediatric Rheumatology) Mansoura University
New Biomarker in JIA.pptx
Objective, Patient And Method:: ? Objective: assess of IL18 and IFN-gamma as diagnostic and a prognostic marker in JIA patients and its correlation to disease activity. ? Patient and method: ?Level of IL 18, IFN gamma, JDAS71 ESR, JDAS71CRP were detected in 45 JIA patients fulfilling (ILAR) 1997 classification criteria. ?Initial visit (basic laboratory, activity marker, level of IL18, IF gamma) were assed. ?Follow up visit, reassess activity marker and level of decrement of JDAS71ESR, JDAS71 CRP, IL18, IF gamma.
Patients (n=45) Characteristics Age (years) (mean¡ÀSD) 11.2¡À3.4 Gender (n%) Female 32(71.1%) Male 13 (28.9%) Family history of autoimmune disease(n%) Positive 4 (8.9%) Negative 41 (91.1%) Duration of arthritis(n%) Less than one year From (1 to 5) years More than 5 years 15 (33%) 21 (47%) 9 (20%) Delay of diagnosis(n%) No delay Delay 6 months Delay 12 months Delay 24 months Delay 36 months 7 (16%) 9 (20%) 8 (18%) 10 (22%) 11 (24%) Figure (1):- JIA types according to ILAR2016 of studied patients- Table (1): Demographic Data Of The Studied Patients n=45:
Table (2): Comparison of patients` symptoms at entry and at end of the study n=45: At entry of the study n (%) At end of the study n (%) P* Morning stiffness (n%) More than one hour 44 (98%) 16 (35.6%) <0.001 Ocular symptoms (n%) Itching 19 (42.2%) 10(22.2%) <0.001 Redness 7(15.6%) 5(11.1%) Active uveitis (n%) Present 3(7%) 0 (0%) 0.25* Absent 42(93%) 45(100%) Knee 43 (95.6%) 32 (71.1%) 0.007 Ankle 38 (84.4%) 21 (46.7%) <0.001 Small joints of the feet 32 (71.1%) 7 (8%) <0.001 Small joints of the hand 32 (71.1%) 12 (26.7%) <0.001 Figure(2) Unilateral swelling in Right knee of young female child. Figure(3): Dactylitis (sausage digit) of both hand of male child.
Table (3): Comparison of laboratory data of studied group at the entry and the end of the study n=45 At entry of the study At the end of the study P* ESR 100 (50-155) 25 (10-52) < 0.001 CRP 30 (10-72) 10 (5-20) < 0.001 S. ferritin 50 (20-880) 20 (10-140) < 0.001 JDAS71ESR (mean ¡ÀSD) 6.7¡À0.8 5.4¡À0.7 <0.001 JDAS71CRP median (IQ) 5.9 (4.4-6.5) 4.9 (4.1-5.5) <0.001 IL18 (pg/ml) 19.2 (9.6-50) 6.1 (0.82-11.38) <0.001 IFN gamma (pg/ml) 18.8 (9.9-35.7) 7.6 (2.6-13.7) <0.001 At entry of study At end of the study p* Steroid (n%) 43 (96%) 37 (82%) 0.032 MTX(n%) 21 (47%) 42 (94%) 0.000 Biological drugs(n%) 1(2%) 26 (58%) 0.000 Table (4):-Comparison of medication at entry and at end of the study n=45:
IL 18 IFN gamma JDAS71ESR JDAS71CRP Rho P* Rho P* Rho P* Rho P* Age 0.008 0.957 -0.013 0.933 0.184 0.227 0.023 0.883 Socioeconomic status -0.165 0.278 -0.401 0.006 -0.279 0.063 -0.349 0.019 Duration of disease -0.234 0.122 0.067 0.662 0.369 0.013 0.294 0.05 Uveitis -0.045 0.771 0.312 0.037 0.272 0.071 0.23 0.128 Delay of diagnosis -0.305 0.041 -0.036 0.816 0.171 0.261 0.171 0.26 S.ferritin 0.001 0.993 -0.013 0.932 0.134 0.38 0.106 0.49 ESR -0.038 0.806 0.209 0.168 0.616 0 0.44 0.003 CRP -0.114 0.457 0.072 0.64 0.496 0.001 0.583 0.001 JDAS71 ESR -0.148 0.331 0.163 0.285 1 0.919 <0.001 JDAS 71 CRP -0.168 0.269 0.1 0.512 0 0.841 1 IL18 level (pg/ml) 1 0.449 0.002* -0.148 0.331 -0.168 0.269 IFN gamma (pg/ml) 0.317 0.034 1 0.163 0.285 0.1 0.512 Table (4):Correlation between IL 18 and IFN gamma, DAS28 ESR and DAS28 CRP with other parameter:
JDAS71ESR Decrement JDAS71CRP Decrement Rho P Rho P Age -0.06 0.72 -0.11 0.46 Steroid dose 0.19 0.21 0.14 0.36 BW -.312* 0.04 -0.25 0.1 Height -.370* 0.01 -0.16 0.3 Ferritin -0.07 0.65 0.04 0.81 HLAB27 -0.22 0.15 -0.09 0.55 ESR 0.13 0.39 0.18 0.24 CRP 0.474** <0.001 .513** <0.001 IL18 (pg/ml) -0.01 0.97 -0.27 0.08 IFN gamma (pg/ml) 0.11 0.47 -0.1 0.51 Table (5): Correlation of JDAS71ERS decrement and JDAS71CRP and different parameters: Figure (5-a) Linear Regression of IL18 in good response group Figure (5-b) Linear Regression of IFN ¨Cgamma level in poor response group:
Good Response Poor Response P* Median (Q1-Q3) Median(Q1-Q3 Ferritin 20.0 (14.3-31.3) 20.0 (20-30) 0.41 ESR 20.0 (14.5-35) 40.0 (30-50) 0.01 CRP 8.0 (5-10) 10.0 (7-15) 0.09 JDAS71ESR 5.3 (4.7-5.7) 5.8 (5.4-6.1) 0.03 JDAS71CRP 4.9 (4.5-5.2) 5.0 (4.8-5.2) 0.40 IL-18 5.2 (2.3-7.9) 9.1 (6.7-10.1) 0.01 IFN-gamma 8.1 (4.7-9.6) 7.3 (5.1-9.4) 0.59 JDAS71ESR Decrement 0.2 (.1-.3) 0.1 (0.1-0.2) 0.03 JDAS71CRP Decrement 0.2 (.1-.2) 0.1 (0.1-0.1) 0.04 IL18 decrement 0.8 (.6-.9) 0.5 (0.3-0.6) 0.01 IFN-gamma decrement 0.7 (.5-.8) 0.5 (0.3-0.7) 0.09 Figure (7) comparison of IL18 decrement between poor and good response patients: Figure (6): Comparison of IFN gamma decrement between poor and good response patients: Table (6): Comparison between Patients with good (30/45) and poor response(15/45):
CONCLUSION: ? IL18 cytokine is a useful biomarker in predicating the disease activity and level of decrement of IL18 was a good predictor of response to the therapy. ? IFN-gamma cytokine is an indicator for response to the therapy, and IFN- gamma decrement was an indicator for good response. ? Good response groups (30/45), rising in IL18 level was associated with little decrease in JDAS71 CRP decrement , while in poor response groups (15/45), rising of IFN- gamma level was associated with lower decrement of JDAS71CRP and easily can predict complication. ? IL18 level was positively correlated with IFN-gamma level in different subtypes JIA; So rising in serum IL18 was associated with rising in IFN- gamma level. ? Response to biological therapy was better correlated to JDAS71 ESR and JDAS71CRP. ? Excess body weight and height were associated with poor response and high disease activity with less decrease in JDAS71 ESR.
Recommendation: ? Health education about JIA raises the public awareness of the disease, then help in early diagnosis, therefore early intervention and management. ? Early referral of complicated JIA patients and early intervention with aggressive therapy, may lead to better prognosis and avoid fetal complication as MAS. ? Obesity should be avoid in pediatric groups to ensure a better response and early remission. ? IL18 and IFN-gamma is a promising marker to detect prognosis and response to therapy. ? Follow up of JIA patient with disease activity index; ESR, CRP, JDAS71 score, also assessment of growth and developmental parameters is crucial part of management.
Reference: ? Petty RE, Cassidy JT. Textbook of pediatric rheumatology. Philadelphia: Saunders Elsevier; 2011. ? Dinarello CA, Novick D, Kim S, Gilles G (2013) Interleukin-18 and IL-18 binding protein. Front Immunol 4: 289.doi: 10.3389/fimmu.2013.00289. ? Gracie JA, Robertson SE, McInnes IB. Interleukin-18.J Leukoc Biol 2003;73:213¨C24. ? Kawaguchi Y, Terajima H, Harigai M et al. Interleukin-18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still¡¯s disease. Arthritis Rheum 2001;44: 1716¨C7. ? Kohno, K., J. Kataoka, T. Ohtsuki, Y. Suemoto, I. Okamoto, M. Usui, M. Ikeda, and M. Kurimoto. 1997. IFN- g -inducing factor (IGIF) is a co-stimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J. Immunol. 158:1541. ? Wei H, Wang D, Qian Y, Liu X, Fan S, Yin HS, Wang X (2014) Structural basis for the specific recognition of IL-18 by its alpha receptor. FEBS Letters 558: 3838¨C 3843. doi:10.1016/ j.febslet.2014.09.019.

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New Biomarker in JIA.pptx

  • 1. New Biomarker In Diagnosis And Follow Up Juvenile Idiopathic Arthritis patients. (Single Center Experience) Marwa Abou Elmaaty Mohamed Mohamed Besar Lecturer of Internal Medicine (Rheumatology Immunology Unit, Pediatric Rheumatology) Mansoura University
  • 3. Objective, Patient And Method:: ? Objective: assess of IL18 and IFN-gamma as diagnostic and a prognostic marker in JIA patients and its correlation to disease activity. ? Patient and method: ?Level of IL 18, IFN gamma, JDAS71 ESR, JDAS71CRP were detected in 45 JIA patients fulfilling (ILAR) 1997 classification criteria. ?Initial visit (basic laboratory, activity marker, level of IL18, IF gamma) were assed. ?Follow up visit, reassess activity marker and level of decrement of JDAS71ESR, JDAS71 CRP, IL18, IF gamma.
  • 4. Patients (n=45) Characteristics Age (years) (mean¡ÀSD) 11.2¡À3.4 Gender (n%) Female 32(71.1%) Male 13 (28.9%) Family history of autoimmune disease(n%) Positive 4 (8.9%) Negative 41 (91.1%) Duration of arthritis(n%) Less than one year From (1 to 5) years More than 5 years 15 (33%) 21 (47%) 9 (20%) Delay of diagnosis(n%) No delay Delay 6 months Delay 12 months Delay 24 months Delay 36 months 7 (16%) 9 (20%) 8 (18%) 10 (22%) 11 (24%) Figure (1):- JIA types according to ILAR2016 of studied patients- Table (1): Demographic Data Of The Studied Patients n=45:
  • 5. Table (2): Comparison of patients` symptoms at entry and at end of the study n=45: At entry of the study n (%) At end of the study n (%) P* Morning stiffness (n%) More than one hour 44 (98%) 16 (35.6%) <0.001 Ocular symptoms (n%) Itching 19 (42.2%) 10(22.2%) <0.001 Redness 7(15.6%) 5(11.1%) Active uveitis (n%) Present 3(7%) 0 (0%) 0.25* Absent 42(93%) 45(100%) Knee 43 (95.6%) 32 (71.1%) 0.007 Ankle 38 (84.4%) 21 (46.7%) <0.001 Small joints of the feet 32 (71.1%) 7 (8%) <0.001 Small joints of the hand 32 (71.1%) 12 (26.7%) <0.001 Figure(2) Unilateral swelling in Right knee of young female child. Figure(3): Dactylitis (sausage digit) of both hand of male child.
  • 6. Table (3): Comparison of laboratory data of studied group at the entry and the end of the study n=45 At entry of the study At the end of the study P* ESR 100 (50-155) 25 (10-52) < 0.001 CRP 30 (10-72) 10 (5-20) < 0.001 S. ferritin 50 (20-880) 20 (10-140) < 0.001 JDAS71ESR (mean ¡ÀSD) 6.7¡À0.8 5.4¡À0.7 <0.001 JDAS71CRP median (IQ) 5.9 (4.4-6.5) 4.9 (4.1-5.5) <0.001 IL18 (pg/ml) 19.2 (9.6-50) 6.1 (0.82-11.38) <0.001 IFN gamma (pg/ml) 18.8 (9.9-35.7) 7.6 (2.6-13.7) <0.001 At entry of study At end of the study p* Steroid (n%) 43 (96%) 37 (82%) 0.032 MTX(n%) 21 (47%) 42 (94%) 0.000 Biological drugs(n%) 1(2%) 26 (58%) 0.000 Table (4):-Comparison of medication at entry and at end of the study n=45:
  • 7. IL 18 IFN gamma JDAS71ESR JDAS71CRP Rho P* Rho P* Rho P* Rho P* Age 0.008 0.957 -0.013 0.933 0.184 0.227 0.023 0.883 Socioeconomic status -0.165 0.278 -0.401 0.006 -0.279 0.063 -0.349 0.019 Duration of disease -0.234 0.122 0.067 0.662 0.369 0.013 0.294 0.05 Uveitis -0.045 0.771 0.312 0.037 0.272 0.071 0.23 0.128 Delay of diagnosis -0.305 0.041 -0.036 0.816 0.171 0.261 0.171 0.26 S.ferritin 0.001 0.993 -0.013 0.932 0.134 0.38 0.106 0.49 ESR -0.038 0.806 0.209 0.168 0.616 0 0.44 0.003 CRP -0.114 0.457 0.072 0.64 0.496 0.001 0.583 0.001 JDAS71 ESR -0.148 0.331 0.163 0.285 1 0.919 <0.001 JDAS 71 CRP -0.168 0.269 0.1 0.512 0 0.841 1 IL18 level (pg/ml) 1 0.449 0.002* -0.148 0.331 -0.168 0.269 IFN gamma (pg/ml) 0.317 0.034 1 0.163 0.285 0.1 0.512 Table (4):Correlation between IL 18 and IFN gamma, DAS28 ESR and DAS28 CRP with other parameter:
  • 8. JDAS71ESR Decrement JDAS71CRP Decrement Rho P Rho P Age -0.06 0.72 -0.11 0.46 Steroid dose 0.19 0.21 0.14 0.36 BW -.312* 0.04 -0.25 0.1 Height -.370* 0.01 -0.16 0.3 Ferritin -0.07 0.65 0.04 0.81 HLAB27 -0.22 0.15 -0.09 0.55 ESR 0.13 0.39 0.18 0.24 CRP 0.474** <0.001 .513** <0.001 IL18 (pg/ml) -0.01 0.97 -0.27 0.08 IFN gamma (pg/ml) 0.11 0.47 -0.1 0.51 Table (5): Correlation of JDAS71ERS decrement and JDAS71CRP and different parameters: Figure (5-a) Linear Regression of IL18 in good response group Figure (5-b) Linear Regression of IFN ¨Cgamma level in poor response group:
  • 9. Good Response Poor Response P* Median (Q1-Q3) Median(Q1-Q3 Ferritin 20.0 (14.3-31.3) 20.0 (20-30) 0.41 ESR 20.0 (14.5-35) 40.0 (30-50) 0.01 CRP 8.0 (5-10) 10.0 (7-15) 0.09 JDAS71ESR 5.3 (4.7-5.7) 5.8 (5.4-6.1) 0.03 JDAS71CRP 4.9 (4.5-5.2) 5.0 (4.8-5.2) 0.40 IL-18 5.2 (2.3-7.9) 9.1 (6.7-10.1) 0.01 IFN-gamma 8.1 (4.7-9.6) 7.3 (5.1-9.4) 0.59 JDAS71ESR Decrement 0.2 (.1-.3) 0.1 (0.1-0.2) 0.03 JDAS71CRP Decrement 0.2 (.1-.2) 0.1 (0.1-0.1) 0.04 IL18 decrement 0.8 (.6-.9) 0.5 (0.3-0.6) 0.01 IFN-gamma decrement 0.7 (.5-.8) 0.5 (0.3-0.7) 0.09 Figure (7) comparison of IL18 decrement between poor and good response patients: Figure (6): Comparison of IFN gamma decrement between poor and good response patients: Table (6): Comparison between Patients with good (30/45) and poor response(15/45):
  • 10. CONCLUSION: ? IL18 cytokine is a useful biomarker in predicating the disease activity and level of decrement of IL18 was a good predictor of response to the therapy. ? IFN-gamma cytokine is an indicator for response to the therapy, and IFN- gamma decrement was an indicator for good response. ? Good response groups (30/45), rising in IL18 level was associated with little decrease in JDAS71 CRP decrement , while in poor response groups (15/45), rising of IFN- gamma level was associated with lower decrement of JDAS71CRP and easily can predict complication. ? IL18 level was positively correlated with IFN-gamma level in different subtypes JIA; So rising in serum IL18 was associated with rising in IFN- gamma level. ? Response to biological therapy was better correlated to JDAS71 ESR and JDAS71CRP. ? Excess body weight and height were associated with poor response and high disease activity with less decrease in JDAS71 ESR.
  • 11. Recommendation: ? Health education about JIA raises the public awareness of the disease, then help in early diagnosis, therefore early intervention and management. ? Early referral of complicated JIA patients and early intervention with aggressive therapy, may lead to better prognosis and avoid fetal complication as MAS. ? Obesity should be avoid in pediatric groups to ensure a better response and early remission. ? IL18 and IFN-gamma is a promising marker to detect prognosis and response to therapy. ? Follow up of JIA patient with disease activity index; ESR, CRP, JDAS71 score, also assessment of growth and developmental parameters is crucial part of management.
  • 12. Reference: ? Petty RE, Cassidy JT. Textbook of pediatric rheumatology. Philadelphia: Saunders Elsevier; 2011. ? Dinarello CA, Novick D, Kim S, Gilles G (2013) Interleukin-18 and IL-18 binding protein. Front Immunol 4: 289.doi: 10.3389/fimmu.2013.00289. ? Gracie JA, Robertson SE, McInnes IB. Interleukin-18.J Leukoc Biol 2003;73:213¨C24. ? Kawaguchi Y, Terajima H, Harigai M et al. Interleukin-18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still¡¯s disease. Arthritis Rheum 2001;44: 1716¨C7. ? Kohno, K., J. Kataoka, T. Ohtsuki, Y. Suemoto, I. Okamoto, M. Usui, M. Ikeda, and M. Kurimoto. 1997. IFN- g -inducing factor (IGIF) is a co-stimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J. Immunol. 158:1541. ? Wei H, Wang D, Qian Y, Liu X, Fan S, Yin HS, Wang X (2014) Structural basis for the specific recognition of IL-18 by its alpha receptor. FEBS Letters 558: 3838¨C 3843. doi:10.1016/ j.febslet.2014.09.019.