Progranulin and insulin-like Growth Factor Binding Protein-2 as Biomarkers of Disease Activity and Pathological Changes in Lupus Nephritis

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease, characterised by the production of auto-antibodies and the formation of immune complexes due to the polyclonal activation of T and B lymphocytes, which results in tissue and organ damage. During inflammation, neutrophils and macrophages release serine proteases to cleave progranulin (PGRN) into granulin, which exerts its pro-inflammatory effects that counteract the anti-inflammatory effects of intact PGRN. It is suggested that insulin-like growth factor binding protein-2 (IGFBP-2) is a dependable biomarker of renal deterioration but it is still unclear if it has high sensitivity and specificity for discriminating SLE-caused kidney disease from other-cause kidney disease.

This study aimed to investigate the diagnostic value of PGRN and ILGFBP-2 in patients with lupus nephritis (LN) and the correlation of these biomarkers with disease activity and renal biopsy pathology.

Patients and methods Patients with SLE (n=25) and chronic kidney disease (CKD) (n=25), and age- and sex-matched controls (n=25) were enrolled in the study. Serum PGRN and ILGFBP-2 levels were measured for each group.

Results Disease duration was 4.78±4.26 years in the SLE patients. The mean SLE Disease Activity Index score was 15.04±7.54. All renal biopsy results were class 2, 3, and 5 with a percentage of 32, 24, and 44% respectively. PGRN and ILGFBP-2 were significantly higher in SLE patients (p<0.001 all) than in the CKD and control groups. All patients with high levels of biomarkers showed higher values of SLE disease activity. No significant difference was noted between active and inactive LN or classes of renal biopsy with PGRN and ILGFBP-2.

Conclusion PGRN and ILGFBP-2 are significantly elevated in SLE compared to CKD and the general population and were associated with the SLE Disease Activity Index but not with active LN or classes of renal biopsy.

Zusammenfassung

Hintergrund Der systemische Lupus erythematodes (SLE) ist eine chronische Autoimmunerkrankung, die durch die Produktion von Autoantikörpern und die Bildung von Immunkomplexen aufgrund der polyklonalen Aktivierung von T- und B-Lymphozyten gekennzeichnet ist, die zu Gewebs- und Organschäden führen. Während der Entzündung können Neutrophile und Makrophagen Serin-Proteasen freisetzen, um Progranulin (PGRN) in Granulin zu spalten, das seine entzündungsfördernden Wirkungen ausübt, die den entzündungshemmenden Wirkungen von intaktem PGRN entgegenwirken. Es wird vorgeschlagen, dass das Insulin-ähnliche Wachstumsfaktor-Bindungsprotein-2 (IGFBP-2) ein verlässlicher Biomarker für die renale Verschlechterung ist, aber es ist immer noch unklar, ob es eine hohe Sensitivität und Spezifität für die Diskriminierung von SLE-verursachter Nierenerkrankung hat. Ziel dieser Studie war es, den diagnostischen Wert von PGRN und ILGFBP-2 bei Patienten mit Lupusnephritis (LN) und die Korrelation dieser Biomarker mit Krankheitsaktivität und Nierenbiopsie-Pathologie zu untersuchen.

Patienten und Methoden In die Studie wurden Patienten mit SLE (n = 25) und chronischer Nierenerkrankung (CKD) (n = 25), Kontroll- und Geschlechtskontrollen (n = 25) eingeschlossen. Die Serum-PGRN- und ILGFBP-2-Spiegel wurden für jede Gruppe gemessen.

Ergebnisse Die Krankheitsdauer betrug bei den SLE-Patienten 4,78 ± 4,26 Jahre. Die mittlere SLEDisease Activity Index erzielte 15,04 ± 7,54. Alle Nierenbiopsieergebnisse waren Klasse 2, 3 und 5 mit einem Prozentsatz von 32%, 24% bzw. 44%. PGRN und ILGFBP-2 waren signifikant höher bei SLE-Patienten (p<0,001all) als in der CKD und Kontrollgruppen. Alle Patienten mit hohen Biomarkern wiesen höhere SLE-Werte auf. Es wurde kein signifikanter Unterschied zwischen aktivem und inaktivem LN oder Klassen der Nierenbiopsie mit PGRN und ILGFBP-2 festgestellt.

Schlussfolgerung PGRN und ILGFBP-2 sind im Vergleich zu CKD und der Allgemeinbevölkerung signifikant erhöht und mit dem SLEDisease-Aktivitätsindex assoziiert, jedoch nicht mit aktiven LN oder Klassen von Nierenbiopsien.

Key words

progranulin (PGRN) - insulin-like growth factor binding protein (IGFBP-2) - lupus nephritis - pathology

Schlüsselwörter

progranulin (PGRN) - Insulin-ähnliches Wachstumsfaktorbindungsprotein (IGFBP-2) - lupus nephritis - Pathologie

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