Metabolic Disturbances Associated with Systemic Lupus Erythematosus

The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid β oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources. Whereas long-chain fatty acids, including the n3 and n6 essential fatty acids, were significantly reduced, medium chain fatty acids and serum free fatty acids were elevated. The SLE metabolome exhibited profound lipid peroxidation, reflective of oxidative damage. Deficiencies were noted in the cellular anti-oxidant, glutathione, and all methyl group donors, including cysteine, methionine, and choline, as well as phosphocholines. The best discriminators of SLE included elevated lipid peroxidation products, MDA, gamma-glutamyl peptides, GGT, leukotriene B4 and 5-HETE. Importantly, similar elevations were not observed in another chronic inflammatory autoimmune disease, rheumatoid arthritis. To sum, comprehensive profiling of the SLE metabolome reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment

Incidence of Systemic Vasculitis and Clinical Outcomes in Systemic Sclerosis: 2-Years Follow-Up of Asymptomatic Positive for Anti-Neutrophilic Cytoplasmic Antibody

Raiwin Suwannamajo, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Chingching Foocharoen Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, ThailandCorrespondence: Chingching Foocharoen, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand, Tel +6643363746, Email [email protected]: Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) overlap with systemic sclerosis (SSc) is uncommon. We aimed to determine the incidence of AAV and define clinical outcomes relevant to asymptomatic screening positive for ANCA in SSc after 2 years of follow-up.Patients and Methods: The study was a cohort study of 185 Thai adult SSc patients testing for ANCA and having a 2-year follow-up at the Scleroderma Clinic, Khon Kaen University, Thailand. The incidence of AAV and outcomes of those who tested positive for ANCA were evaluated.Results: A total of 185 SSc patients were tested for ANCA, of whom 21.6% were positive for either cytoplasmic ANCA, perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), or anti-proteinase3 antibody. Only one 52-year-old female patient with dcSSc, negative for initial ANCA test, developed AAV (microscopic polyangiitis) 7 months after the first ANCA test for an incidence of AAV of 0.27 per 100-person-years (95% CI 0.01– 1.5). She was positive for p-ANCA and anti-MPO. Eight of those who had an initial test were positive for ANCA and underwent a repeated test. Only two cases persisted as positive for ANCA (1 anti-MPO and 1 anti-PR3) and had no clinicals suspicious of vasculitis. Four cases that had ANCA turned to a negative result.Conclusion: AAV is a rare complication in SSc, so ANCA may not have any role as a screening test for AAV as it cannot predict the development of AAV in SSc. We suggest testing for ANCA only in SSc patients with clinicals suspicious of AAV.Keywords: systemic sclerosis, scleroderma, anti-neutrophilic cytoplasmic antibody, ANCA- associated vasculitis, vasculiti

The prevalence and clinical features associated of hypothyroidism among Thai systemic sclerosis patients

Thyroid disease, particularly hypothyroidism, has been reported in systemic sclerosis (SSc). Some clinical features of SSc can also present in hypothyroidism. Our aims were to determine the prevalence of, and describe clinical features associated with, hypothyroidism in SSc patients. We conducted a historical cohort study of adult SSc patients who underwent screening thyroid function tests at the Scleroderma Clinic, Khon Kaen University, Thailand, between 2009 and 2018. The patients who had any thyroid disorders before the onset of SSc and were diagnosed as an overlap syndrome were excluded. A total of 200 SSc were included according to sample size calculation, among whom the female to male ratio was 2:1. The majority of cases (137; 69.5%) were diffuse cutaneous SSc subset. The mean age was 55.8 ± 10.7 years and the median duration of disease 4.9 (IQR 1.6–9.9) years. Of the total, 9 had primary hypothyroidism (prevalence 4.5%; 95%CI 2.1–8.4) and 22 had subclinical hypothyroidism (prevalence 11%; 95%CI 7.0–16.2). Of the latter 22, 71% had dcSSc. Logistic regression analysis indicated that unexplained anemia was significantly associated with either subclinical hypothyroid or hypothyroidism (OR 2.74; 95% CI 1.17–6.47), whereas Raynaud’s phenomenon had a negative association (OR 0.28; 95% CI 0.11–0.66). Neither severity of skin tightness nor internal organ involvement were associated with hypothyroidism among SSc patients. Clinical-subclinical hypothyroidism is uncommon among SSc patients, it is frequently associated with anemia, and less so Raynaud’s phenomenon. Clinical-subclinical hypothyroidism should thus be considered in cases of unexplained anemia in SSc patients