Skip to main content
Erschienen in: Clinical Rheumatology 11/2018

13.07.2018 | Original Article

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis

verfasst von: Arwa Mohammad Hassan, Nessma Mohamed Ahmed Farghal, Doaa Salah Hegab, Wesam Salah Mohamed, Hend Hassan Abd-Elnabi

Erschienen in: Clinical Rheumatology | Ausgabe 11/2018

Einloggen, um Zugang zu erhalten

Abstract

Juvenile systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease of unpredicted course and prognosis. Rates of organ involvement in SLE are higher in children, and overt lupus nephropathy is more often a presenting manifestation of SLE in children than adults. Inflammatory soluble chemokine CXC motif-ligand 16 (sCXCL16) is an important pathogenic mediator in inflammatory diseases as SLE. Herein, we aimed to evaluate serum level of sCXCL16 in jSLE patients in comparison to healthy controls and to correlate it with disease activity and extent of cutaneous and renal affection, to detect its possible role in disease pathogenesis. Serum level of sCXCL16 was determined by ELISA in 27 patients with jSLE (mean age 12.35 years ± 2.26 SD) in addition to 30 age- and sex-matched healthy controls and correlated with clinical and laboratory parameters in lupus group. Serum sCXCL16 was significantly higher in jSLE patients than controls (P ≤ 0.001), and it correlated positively with SLE disease activity, severity of lupus nephritis, 24-h urinary protein, anti-dsDNA titre, blood pressure, and ESR, while it correlated negatively with serum C3 levels. Serum sCXCL16 was higher in jSLE patients with alopecia and malar erythema. Serum sCXCL16 might play a role in inflammatory pathogenesis of jSLE particularly in periods of disease activity. It might serve as a future useful laboratory test for detection of jSLE activity, renal insult, and its severity which might limit the need for invasive renal biopsies in such a delicate patient population.
Literatur
1.
Zurück zum Zitat Cunha JS, Gilek-Seibert K (2016) Systemic lupus erythematosus: a review of the clinical approach to diagnosis and update on current targeted therapies. R I Med J (2013) 99(12):23–27 Cunha JS, Gilek-Seibert K (2016) Systemic lupus erythematosus: a review of the clinical approach to diagnosis and update on current targeted therapies. R I Med J (2013) 99(12):23–27
2.
Zurück zum Zitat Teruel M, Alarcón-Riquelme ME (2016) The genetic basis of systemic lupus erythematosus: what are the risk factors and what have we learned. J Autoimmun 74:161–175CrossRef Teruel M, Alarcón-Riquelme ME (2016) The genetic basis of systemic lupus erythematosus: what are the risk factors and what have we learned. J Autoimmun 74:161–175CrossRef
3.
Zurück zum Zitat Klein-Gitelman M, Reiff A, Silverman ED (2002) Systemic lupus erythematosus in childhood. Rheum Dis Clin N Am 28(561–77):vi–vii Klein-Gitelman M, Reiff A, Silverman ED (2002) Systemic lupus erythematosus in childhood. Rheum Dis Clin N Am 28(561–77):vi–vii
4.
Zurück zum Zitat Klein-Gitelman MS, Miller ML (1996) Systemic lupus erythematosus. Indian J Pediatr 63(4):485–500CrossRef Klein-Gitelman MS, Miller ML (1996) Systemic lupus erythematosus. Indian J Pediatr 63(4):485–500CrossRef
5.
Zurück zum Zitat Abdel-Hafez MA, Abdel-Nabi H (2015) Juvenile systemic lupus erythematosus: onset patterns and short-term outcome in Egyptian children, a single-center experience. Lupus 24(13):1455–1461CrossRef Abdel-Hafez MA, Abdel-Nabi H (2015) Juvenile systemic lupus erythematosus: onset patterns and short-term outcome in Egyptian children, a single-center experience. Lupus 24(13):1455–1461CrossRef
6.
Zurück zum Zitat Allen SJ, Crown SE, Handel TM (2007) Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 25:787–820CrossRef Allen SJ, Crown SE, Handel TM (2007) Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 25:787–820CrossRef
7.
Zurück zum Zitat van Lieshout AW, van der Voort R, Toonen LW, van Helden SF, Figdor CG, van Riel PL, Radstake TR, Adema GJ (2009) Regulation of CXCL16 expression and secretion by myeloid cells is not altered in rheumatoid arthritis. Ann Rheum Dis 68(6):1036–1043CrossRef van Lieshout AW, van der Voort R, Toonen LW, van Helden SF, Figdor CG, van Riel PL, Radstake TR, Adema GJ (2009) Regulation of CXCL16 expression and secretion by myeloid cells is not altered in rheumatoid arthritis. Ann Rheum Dis 68(6):1036–1043CrossRef
8.
Zurück zum Zitat Petit SJ, Wise EL, Chambers JC, Sehmi J, Chayen NE, Kooner JS, Pease JE (2011) The CXCL16 A181V mutation selectively inhibits monocyte adhesion to CXCR6 but is not associated with human coronary heart disease. Arterioscler Thromb Vasc Biol 31:914–920CrossRef Petit SJ, Wise EL, Chambers JC, Sehmi J, Chayen NE, Kooner JS, Pease JE (2011) The CXCL16 A181V mutation selectively inhibits monocyte adhesion to CXCR6 but is not associated with human coronary heart disease. Arterioscler Thromb Vasc Biol 31:914–920CrossRef
9.
Zurück zum Zitat Borst O, Schaub M, Walker B, Sauter M, Muenzer P, Gramlich M, Mueller K, Geisler T, Lang F, Klingel K, Kandolf R, Bigalke B, Gawaz M, Zuern CS (2014) CXCL16 is a novel diagnostic marker and predictor of mortality in inflammatory cardiomyopathy and heart failure. Int J Cardiol 176(3):896–903CrossRef Borst O, Schaub M, Walker B, Sauter M, Muenzer P, Gramlich M, Mueller K, Geisler T, Lang F, Klingel K, Kandolf R, Bigalke B, Gawaz M, Zuern CS (2014) CXCL16 is a novel diagnostic marker and predictor of mortality in inflammatory cardiomyopathy and heart failure. Int J Cardiol 176(3):896–903CrossRef
10.
Zurück zum Zitat Qin M, Guo Y, Jiang L, Wang X (2014) Elevated levels of serum sCXCL16 in systemic lupus erythematosus; potential involvement in cutaneous and renal manifestations. ClinRheumatol 33(11):1595–1601 Qin M, Guo Y, Jiang L, Wang X (2014) Elevated levels of serum sCXCL16 in systemic lupus erythematosus; potential involvement in cutaneous and renal manifestations. ClinRheumatol 33(11):1595–1601
11.
Zurück zum Zitat Matloubian M, David A, Engel S, Ryan JE, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1:298–304CrossRef Matloubian M, David A, Engel S, Ryan JE, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1:298–304CrossRef
12.
Zurück zum Zitat Borst O, Abed M, Alesutan I, Towhid ST, Qadri SM, Föller M, Gawaz M, Lang F (2012) Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX. Am J Physiol Cell Physiol 302:C644–C651CrossRef Borst O, Abed M, Alesutan I, Towhid ST, Qadri SM, Föller M, Gawaz M, Lang F (2012) Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX. Am J Physiol Cell Physiol 302:C644–C651CrossRef
13.
Zurück zum Zitat Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, Schuster B, Kallen KJ, Saftig P, Rose-John S, Ludwig A (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol 172:6362–6372CrossRef Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, Schuster B, Kallen KJ, Saftig P, Rose-John S, Ludwig A (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol 172:6362–6372CrossRef
14.
Zurück zum Zitat Kim CH, Kunkel EJ, Boisvert J, Johnston B, Campbell JJ, Genovese MC, Greenberg HB, Butcher EC (2001) Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest 107:595–601CrossRef Kim CH, Kunkel EJ, Boisvert J, Johnston B, Campbell JJ, Genovese MC, Greenberg HB, Butcher EC (2001) Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest 107:595–601CrossRef
15.
Zurück zum Zitat Van d V, van Lieshout AW, Toonen LW, Sloetjes AW, van den Berg WB, Figdor CG et al (2005) Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid joints. Arthritis Rheum 52:1381–1391CrossRef Van d V, van Lieshout AW, Toonen LW, Sloetjes AW, van den Berg WB, Figdor CG et al (2005) Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid joints. Arthritis Rheum 52:1381–1391CrossRef
16.
Zurück zum Zitat Sato T, Thorlacius H, Johnston B, Staton TL, Xiang W, Littman DR, Butcher EC (2005) Role for CXCR6 in recruitment of activated CD8+ lymphocytes to inflamed liver. J Immunol 174:277–283CrossRef Sato T, Thorlacius H, Johnston B, Staton TL, Xiang W, Littman DR, Butcher EC (2005) Role for CXCR6 in recruitment of activated CD8+ lymphocytes to inflamed liver. J Immunol 174:277–283CrossRef
17.
Zurück zum Zitat Gutwein P, Abdel-Bakky MS, Schramme A, Doberstein K, Kampfer-Kolb N, Amann K et al (2009) CXCL16 is expressed in podocytes and acts as a scavenger receptor for oxidized low-density lipoprotein. Am J Pathol 174:2061–2072CrossRef Gutwein P, Abdel-Bakky MS, Schramme A, Doberstein K, Kampfer-Kolb N, Amann K et al (2009) CXCL16 is expressed in podocytes and acts as a scavenger receptor for oxidized low-density lipoprotein. Am J Pathol 174:2061–2072CrossRef
18.
Zurück zum Zitat Izquierdo MC, Sanz AB, Mezzano S, Blanco J, Carrasco S, Sanchez-Nino MD et al (2012) TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubule-interstitial inflammation. Kidney Int 81:1098–1107CrossRef Izquierdo MC, Sanz AB, Mezzano S, Blanco J, Carrasco S, Sanchez-Nino MD et al (2012) TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubule-interstitial inflammation. Kidney Int 81:1098–1107CrossRef
19.
Zurück zum Zitat Izquierdo MC, Martin-Cleary C, Fernandez-Fernandez B, Elewa U, Sanchez-Niño MD, Carrero JJ, Ortiz A (2014) CXCL16 in kidney and cardiovascular injury. Cytokine Growth Factor Rev 25(3):317–325CrossRef Izquierdo MC, Martin-Cleary C, Fernandez-Fernandez B, Elewa U, Sanchez-Niño MD, Carrero JJ, Ortiz A (2014) CXCL16 in kidney and cardiovascular injury. Cytokine Growth Factor Rev 25(3):317–325CrossRef
20.
Zurück zum Zitat Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRef
21.
Zurück zum Zitat Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM, American College of Rheumatology (2012) American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 64(6):797–808CrossRef Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM, American College of Rheumatology (2012) American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 64(6):797–808CrossRef
22.
Zurück zum Zitat Churg J, Sobin LH (1982) Lupus nephritis. Renal disease, classification and atlas of glomerular diseases. Igaku-Shoin, New York, pp 127–149 Churg J, Sobin LH (1982) Lupus nephritis. Renal disease, classification and atlas of glomerular diseases. Igaku-Shoin, New York, pp 127–149
23.
Zurück zum Zitat Gladman DD, Lbanez D, Urowitz MB (2000) Systemic lupus erythematosus Disease Activity Index 2000. J Rheumatol 29:288–291 Gladman DD, Lbanez D, Urowitz MB (2000) Systemic lupus erythematosus Disease Activity Index 2000. J Rheumatol 29:288–291
24.
Zurück zum Zitat Pluchinotta FR, Schiavo B, Vittadello F, Martini G, Perilongo G, Zulian F (2007) Distinctive clinical features of pediatric systemic lupus erythematosus in three different age classes. Lupus 16:550–555CrossRef Pluchinotta FR, Schiavo B, Vittadello F, Martini G, Perilongo G, Zulian F (2007) Distinctive clinical features of pediatric systemic lupus erythematosus in three different age classes. Lupus 16:550–555CrossRef
25.
Zurück zum Zitat Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED (2008) Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. Pediatr 152:550–556CrossRef Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED (2008) Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. Pediatr 152:550–556CrossRef
26.
Zurück zum Zitat Bakr A (2005) Epidemiology treatment and outcome of childhood systemic lupus erythematosus in Egypt. PediatrNephrol 20:1081–1086 Bakr A (2005) Epidemiology treatment and outcome of childhood systemic lupus erythematosus in Egypt. PediatrNephrol 20:1081–1086
27.
Zurück zum Zitat Salah S, Lotfy HM, Sabry SM, El Hamshary A, Taher H (2009) Systemic lupus erythematosus in Egyptian children. Rheumatol Int 29:1463–1468CrossRef Salah S, Lotfy HM, Sabry SM, El Hamshary A, Taher H (2009) Systemic lupus erythematosus in Egyptian children. Rheumatol Int 29:1463–1468CrossRef
28.
Zurück zum Zitat Dung NT, Loan HT, Nielsen S, Zak M, Petersen FK (2012) Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children. Pediatr Rheumatol 10:38–43CrossRef Dung NT, Loan HT, Nielsen S, Zak M, Petersen FK (2012) Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children. Pediatr Rheumatol 10:38–43CrossRef
29.
Zurück zum Zitat Manzi S (2001) Epidemiology of systemic lupus erythematosus. Manag Care 7(16 Suppl):S474–S479 Manzi S (2001) Epidemiology of systemic lupus erythematosus. Manag Care 7(16 Suppl):S474–S479
30.
Zurück zum Zitat Pattaragarn A, Sumboonnanonda A, Parichatikanond P, Supavekin S, Suntornpoch V, Vongjirad A (2005) Systemic lupus erythematosus in Thai children: clinicopathologic findings and outcome in 82 patients. J Med Assoc Thail 8:232–241 Pattaragarn A, Sumboonnanonda A, Parichatikanond P, Supavekin S, Suntornpoch V, Vongjirad A (2005) Systemic lupus erythematosus in Thai children: clinicopathologic findings and outcome in 82 patients. J Med Assoc Thail 8:232–241
31.
Zurück zum Zitat Ramirez Gomez LA, Uribe Uribe O, Osio Uribe O, Grisales Romero H, Cardiel MH, Wojdyla D et al (2008) Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children. Lupus 17:596–604CrossRef Ramirez Gomez LA, Uribe Uribe O, Osio Uribe O, Grisales Romero H, Cardiel MH, Wojdyla D et al (2008) Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children. Lupus 17:596–604CrossRef
32.
Zurück zum Zitat Garcia GE, Truong LD, Zhang P, Johnson RJ, Wilson CB, Feng L et al (2007) Inhibition of CXCL16 attenuates inflammatory and progressive phases of anti-glomerular basement membrane antibody-associated glomerulonephritis. Am J Pathol 170(5):1485–1496CrossRef Garcia GE, Truong LD, Zhang P, Johnson RJ, Wilson CB, Feng L et al (2007) Inhibition of CXCL16 attenuates inflammatory and progressive phases of anti-glomerular basement membrane antibody-associated glomerulonephritis. Am J Pathol 170(5):1485–1496CrossRef
33.
Zurück zum Zitat Wu T, Xie C, Wang HW, Zhou XJ, Schwartz N, Calixto S, Mackay M, Aranow C, Putterman C, Mohan C (2007) Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis. J Immunol 179(10):7166–7175CrossRef Wu T, Xie C, Wang HW, Zhou XJ, Schwartz N, Calixto S, Mackay M, Aranow C, Putterman C, Mohan C (2007) Elevated urinary VCAM-1, P-selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis. J Immunol 179(10):7166–7175CrossRef
34.
Zurück zum Zitat Wen S, He F, Zhu X, Yuan S, Liu H, Sun L (2018) IFN-γ, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus. Clin Exp Rheumatol 36(1):36–43PubMed Wen S, He F, Zhu X, Yuan S, Liu H, Sun L (2018) IFN-γ, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus. Clin Exp Rheumatol 36(1):36–43PubMed
35.
Zurück zum Zitat Gedalia A, Molina JF, Molina J, Uribe O, Malagon C, Espinoza LR (1999) Childhood-onset systemic lupus erythematosus: a comparative study of African-Americans and Latin Americans. Natl Med Assoc 91:497–501 Gedalia A, Molina JF, Molina J, Uribe O, Malagon C, Espinoza LR (1999) Childhood-onset systemic lupus erythematosus: a comparative study of African-Americans and Latin Americans. Natl Med Assoc 91:497–501
36.
Zurück zum Zitat Kole AK, Ghosh A (2009) Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center. Indian J Dermatol 54(2):132–136CrossRef Kole AK, Ghosh A (2009) Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center. Indian J Dermatol 54(2):132–136CrossRef
37.
Zurück zum Zitat Bertsias GK, Ioannidis JP, Aringer M, Bollen E, Bombardieri S, Bruce IN et al (2010) EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 69:2074–2823CrossRef Bertsias GK, Ioannidis JP, Aringer M, Bollen E, Bombardieri S, Bruce IN et al (2010) EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 69:2074–2823CrossRef
38.
Zurück zum Zitat Xia Y, Entman ML, Wang Y (2013) Critical role of CXCL16 in hypertensive kidney injury and fibrosis. Hypertension 62:1129–1137CrossRef Xia Y, Entman ML, Wang Y (2013) Critical role of CXCL16 in hypertensive kidney injury and fibrosis. Hypertension 62:1129–1137CrossRef
39.
Zurück zum Zitat Ting CK, Hsieh KH (1992) A long-term immunological study of childhood onset systemic lupus erythematosus. Ann Rheum Dis 51(1):45–51CrossRef Ting CK, Hsieh KH (1992) A long-term immunological study of childhood onset systemic lupus erythematosus. Ann Rheum Dis 51(1):45–51CrossRef
40.
Zurück zum Zitat Ricker DM, Hebert LA, Rohde R, Sedmak DD, Lewis EJ, Clough JD (1991) Serum C3 levels are diagnostically more sensitive and specific for systemic lupus erythematosus activity than are serum C4 levels. The Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 18(6):678–685CrossRef Ricker DM, Hebert LA, Rohde R, Sedmak DD, Lewis EJ, Clough JD (1991) Serum C3 levels are diagnostically more sensitive and specific for systemic lupus erythematosus activity than are serum C4 levels. The Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 18(6):678–685CrossRef
Metadaten
Titel
Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis
verfasst von
Arwa Mohammad Hassan
Nessma Mohamed Ahmed Farghal
Doaa Salah Hegab
Wesam Salah Mohamed
Hend Hassan Abd-Elnabi
Publikationsdatum
13.07.2018
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 11/2018
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-018-4203-2

Weitere Artikel der Ausgabe 11/2018

Clinical Rheumatology 11/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.