Complement regulator factor H in multiple sclerosis

Ingram, Gillian; Hakobyan, Svetlana; Loveless, Samantha; Robertson, Neil; Morgan, B. Paul

doi:10.1002/jcb.23204

Cited by 10 publications

(9 citation statements)

References 3 publications

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“…The elevated levels of adipsin in our PPMS patients most likely reflect peripheral immune activation and do not associate with ongoing focal CNS changes seen on MRI. Notably, recently the other member of complement pathway, that is, complement factor H, was found to be elevated in sera of patients with progressive MS but not in RRMS or healthy controls [ 39 ]. Together the available data suggest that elevated levels of adipsin in patients with progressive MS reflect ongoing peripheral immune activation.…”

Section: Discussionmentioning

confidence: 99%

Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines

Natarajan

Hagman

Hämäläinen

et al. 2015

Multiple Sclerosis International

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Background and Objective. The role of adipokines in regulation of immune responses has been recognized, but very little is known about their impact on multiple sclerosis (MS). In this study, we analysed whether the major adipokines are differentially expressed in plasma of patients with different MS subtypes and clinically isolated syndrome (CIS) and explored their association with major disease characteristics. Methods. The levels of adiponectin, adipsin, leptin, and resistin in the plasma of 80 patients with different subtypes of MS and CIS were followed up annually over the two years. The data obtained were correlated with disease activity, EDSS and volumes of T1-weighted lesions (T1-LV), and fluid attenuation inversion recovery lesions (FLAIR-LV) on MRI. Results. In MS group, a correlation was found between the level of adipsin and EDSS score at baseline (r = 0.506, p < 0.001). In RRMS, the levels of adipsin correlated with EDSS scores (r = 0.542, p = 0.002), T1-LV (r = 0.410, p = 0.034), and FLAIR-LV (r = 0.601, p = 0.0001) at baseline and an increase in the T1-LV over the follow-up (r = 0.582, p = 0.003). Associations with other adipokines were not detected. Conclusion. Our exploratory study provides novel insights on the impact of adipokines in MS and suggests that adipsin exerts predictive potential as a biomarker of neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines

Natarajan

Hagman

Hämäläinen

et al. 2015

Multiple Sclerosis International

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“…It is noteworthy that Ingram et al recently suggested that elevated complement factor H is a biomarker of multiple sclerosis disease state. 21 …”

Section: Methodsmentioning

confidence: 99%

The relationship of circulating proteins in early pregnancy with preterm birth

Lynch

Wagner

Deterding

et al. 2016

American Journal of Obstetrics and Gynecology

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BACKGROUND Preterm birth (PTB) (<37 completed weeks gestation) is a pathological outcome of pregnancy and a major global health problem. Babies born preterm have an elevated risk for long term adverse medical and neurodevelopmental sequelae. Substantial evidence implicates intrauterine infection and/or inflammation in PTB. However, these are often relatively late findings in the process, when PTB is inevitable. Identification of earlier markers of PTB may make successful intervention possible. Although select proteins, notably, those related to the inflammatory pathways, have been associated with PTB, there has been a lack of research into the role of other protein pathways in the development of PTB. The purpose of this study was to investigate, using a previously described biomarker discovery approach, a subset of circulating proteins and their association with PTB focusing on samples from early pregnancy. OBJECTIVES 1) To perform a large-scale biomarker discovery, utilizing an innovative platform to identify proteins associated with preterm birth in plasma taken between 10 and 15 weeks’ gestation and, 2) To determine which protein pathways are most strongly associated with preterm birth. To address these aims we measured 1129 proteins in a plasma sample from early pregnancy using a multiplexed aptamer–based proteomic technology developed in Colorado by SomaLogic. STUDY DESIGN Using a nested case-control approach, we measured proteins at a single time point in early pregnancy in 41 women who subsequently delivered preterm and 88 women who had term uncomplicated deliveries. We measured 1129 proteins using a multiplexed aptamer–based proteomic technology developed by SomaLogic. Logistic regressions and random forests were used to compare protein levels. RESULTS The complement factors B and H and the coagulation factors IX and IX ab were the highest ranking proteins distinguishing cases of preterm birth from term controls. The top 3 pathways associated with preterm birth were the complement cascade, the immune system and the clotting cascade. CONCLUSIONS Using a discovery approach, these data provide further confirmation that there is an association of immune and coagulation–related events in early pregnancy with preterm birth. Thus, plasma protein profiles at 10–15 weeks of gestation are related to the development of preterm birth later in pregnancy.

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“…In patients with relapse, a small and transient, but significant, increase in factor H concentration has been detected when compared to controls [28]. In addition, quantifying factor H levels in CSF indicated no change during active disease but significantly raised levels in progressive MS [29]. However, Li et al have found a decrease in the expression of factor H in the CSF of RRMS patients with active disease when compared to controls [23].…”

Section: Introductionmentioning

confidence: 99%

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

et al. 2017

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Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability. Furthermore, increased levels of factor H can predict the transition from relapsing to progressive disease, since factor H levels have been found to increase progressively with disease progression over a 2-year period in patients transitioning from RRMS to secondary progressive (SP) MS. In addition, elevations in C3 are seen in primary progressive (PP) MS. Complement components can also differentiate RRMS from neuromyelitis optica. Response gene to complement (RGC)-32, a novel molecule induced by complement activation, is a possible biomarker of relapse and response to glatiramer acetate (GA) therapy, since RGC-32 mRNA expression is significantly decreased during relapse and increased in responders to GA treatment. The predictive accuracy of RGC-32 as a potential biomarker (by ROC analysis) is 90% for detecting relapses and 85% for detecting a response to GA treatment. Thus, complement components can serve as biomarkers of disease activity to differentiate MS subtypes and to measure response to therapy.

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Complement regulator factor H in multiple sclerosis

Cited by 10 publications

References 3 publications

Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines

Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines

The relationship of circulating proteins in early pregnancy with preterm birth

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

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