Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis.

OBJECTIVES: Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. METHODS: We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. RESULTS: We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. CONCLUSION: Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies.

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.

Formation and glomerular deposition of immune complexes in mice administered bovine serum albumin: Evaluation of dose, frequency, and biomarkers.

In preclinical toxicity studies, species-foreign proteins administered to animals frequently leads to formation of anti-drug antibodies (ADA). Such antibodies may form circulating immune complexes (CIC) with the administered protein. These CIC can activate the classical complement pathway, thereby forming complement-bound CIC (cCIC); if large of amounts of CIC or cCIC is formed, the clearance mechanism may become saturated which potentially leads to vascular immune complex (IC) deposition and inflammation. Limited information is available on the effect of different treatment related procedures as well as biomarkers of IC-related vascular disease. In order to explore the effect of different dose regimens on IC formation and deposition, and identification of possible biomarkers of IC deposition and IC-related pathological changes, C57BL/6J and BALB/c mice were dosed subcutaneously twice weekly with bovine serum albumin (BSA) for 13 weeks without adjuvant. After 6 and 13 weeks, CIC and cCIC were detected in plasma; after 13 weeks, IC deposition was detected in kidney glomeruli. In particular immunohistochemistry double-staining was shown to be useful for detection of IC deposition. Increasing dosing frequency or changing BSA dose level on top of an already established CIC and cCIC response did not cause changes in IC deposition, but CIC and cCIC concentrations tended to decrease with increased dose level, and increased cCIC formation was observed after more frequent dosing. The presence of CIC in plasma was associated with glomerular IC deposits in the dose regimen study; however, the use of CIC or cCIC as potential biomarkers for IC deposition and IC-related pathological changes, needs to be explored further.

Association of serum high mobility group box 1 levels with disease activity and renal involvement in patients with systemic vasculitis.

High mobility group box 1 (HMGB1) is a kind of proinflammatory mediator that acts as an alarmin when released by dying, injured or activated cells. Previous studies have reported that HMGB1 are closely linked to antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The present study aimed to evaluate whether serum HMGB1 levels were associated with systemic vasculitis (VAs).The study population consisted of 51 patients with VAs, 46 patients with essential hypertension (EH) and 46 healthy controls (HC). Thirty-five patients with VAs had in active stage and 16 patients with VAs in an inactive stage. Furthermore, 31 patients with VAs had renal involvement, the other 20 patients were selected for without renal involvement. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Associations between serum HMGB1 levels with clinical and laboratory parameters were analyzed.Serum HMGB1 levels in patients with VAs were significantly higher than in EH and HC (all P < .05), and no difference regarding serum HMGB1 levels could be found between EH and HC (P = .208). Serum HMGB1 levels in VAs patients with active stage were significantly higher than those in HC and VAs patients with inactive stage (all P < .05). Patients with renal involvement and non-renal involvement had increased HMGB1 levels compared with HC (all P < .05). In addition, serum HMGB1 levels were significantly higher in patients with renal involvement compared with non-renal involvement patients (P = .001). Correlation analysis showed that serum HMGB1 levels were positive significant correlated with the Birmingham Vasculitis Activity Score, hypersensitive C reactive protein (Hs-CRP), serum creatinine (Scr) and 24-hour proteinuria (all P < .05). Among the subsets of VAs, serum HMGB1 levels were significantly higher in AAV, polyarteritis nodosa (PAN) and takayasu arteritis (TA) than in HC (all P < .05). More interestingly, serum HMGB1 were significantly higher in patients with PAN compared with AAV and TA patients (all P < .05). Furthermore, there was positive correlation between serum HMGB1 levels and Hs-CRP, Scr, and 24-hour proteinuria in patients with PAN (all P < .05).Serum HMGB1 levels are increased in patients with VAs compared with HC and EH and can reflect the disease activity and renal involvement.

Increased Serum MCP-1 Levels in Systemic Vasculitis Patients with Renal Involvement.

Monocyte chemotactic protein 1 (MCP-1) plays a significant role in inflammation pathways by affecting monocyte/macrophage migration, the number of monocytes and T lymphocytes, and osmosis. Inflammation is closely linked to various types of systematic vasculitis. Here we characterized serum MCP-1 levels in systemic vasculitis patients. This cross-sectional study included serum samples collected from 43 patients with systemic vasculitis and 43 healthy controls (HCs). Serum MCP-1 levels in the samples were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Serum MCP-1 levels were significantly higher in patients with systemic vasculitis relative to HCs (parentheses indicate quartile values) [134.65 (73.74, 262.75) pg/mL versus 59.1 (37.41, 90.18) pg/mL, P < 0.001]. Furthermore, systemic vasculitis patients having renal involvement had significantly higher MCP-1 levels relative to patients without renal involvement [196.16 (104.41, 310.35) pg/mL versus 73.74 (41.24, 145.95) pg/mL, P = 0.001] and HCs [196.16 (104.41, 310.35) pg/mL versus 59.10 (37.41, 90.18) pg/mL, P < 0.001]. Serum MCP-1 levels in systemic vasculitis patients were positively correlated with serum creatinine levels (r = 0.387, P < 0.010) and with 24-h proteinuria (r = 0.404, P < 0.014). Receiver operating characteristic (ROC) analysis showed that the cutoff value for MCP-1 to distinguish systemic vasculitis from HCs was 72.73 pg/mg, and the area under the ROC curve was 0.772. The sensitivity and specificity were 76.7% and 72.1%, respectively. Serum MCP-1 levels were significantly higher in patients with systemic vasculitis than in HCs, especially in patients with renal involvement. Thus, serum MCP-1 has the potential to be a biomarker for systemic vasculitis with renal involvement.

HCV-unrelated cryoglobulinaemic vasculitis: the results of a prospective observational study by the Italian Group for the Study of Cryoglobulinaemias (GISC).

OBJECTIVES: To investigate the clinical and laboratory patterns of HCV-unrelated cryoglobulinaemic vasculitis (CV), and the factors influencing its outcome. METHODS: Prospective study of all anti-HCV and HCV-RNA negative patients with CV who have been observed since January 2004 in 17 centres participating in the Italian Group for the Study of Cryoglobulinaemias (GISC). RESULTS: 175 enrolled were followed up for 677 person-years. The associated conditions were primary Sjögren's syndrome (21.1%), SLE (10.9%), other autoimmune disorders (10.9%), lymphoproliferative diseases (6.8%), solid tumours (2.3%) and HBsAg positivity (8.6%), whereas 69 patients (39.4%) had essential CV. There were significant differences in age (p<0.001), gender (p=0.002), the presence of purpura (p=0.005), arthralgia (p=0.009), liver abnormalities (p<0.001), sicca syndrome (p<0.001), lymphadenopathy (p=0.003), splenomegaly (p=0.002), and rheumatoid factor titres (p<0.001) among these groups. Type II mixed cryoglobulins were present in 96 cases (54.9%) and were independently associated with purpura and fatigue (odds ratio [OR]4.3; 95% confidence interval [CI] 1.8-10.2; p=0.001; and OR2.8; 95%CI 1.3-6.3; p=0.012). Thirty-one patients died during follow-up, a mortality rate of 46/1000 person-years. Older age (for each additional year, adjusted hazard ratio [aHR] 1.13; 95%CI 1.06-1.20; p<0.001), male gender (aHR 3.45; 95%CI 1.27-9.40; p=0.015), type II MCG (aHR 3.31; 95%CI 0.09-1.38; p=0.047) and HBsAg positivity (aHR 7.84; 95%CI 1.20-36.04; p=0.008) were independently associated with greater mortality. CONCLUSIONS: HCV-unrelated CV is a multifaceted and often disabling disorder. The associated conditions influence its clinical severity, giving rise to significantly different clinical and laboratory profiles and outcomes.

A case of false positive Troponin I in a patient affected by cryoglobulinemic vasculitis.

Troponin I (TnI) false positive results have been reported in patients affected by immune disorders. We report the case of a 74-year-old woman affected by cryoglobulinemic vasculitis, admitted to the Emergency Room because of a lipotimic episode. A marked elevation of TnI plasma concentration was confirmed in multiple determinations, despite the absence of symptoms or electrocardiogram findings suggesting myocardial infarction. TnI plasma concentration was reported normal after re-testing with a different commercial kit. A false TnI positivity should be considered in patients with immune disorders, especially if seropositive for rheumatoid factor, when the clinical context does not suggest myocardial infarction.

One year in review 2017: systemic vasculitis.

Systemic vasculitis is a group of heterogeneous, disabling disorders. Great interest has recently arisen in pathophysiology, clinical phenotypes and therapy of large- and small-vessel vasculitis. The general work hypothesis has been to promote research focused on disease-related pathogenetic pathways, with the ultimate goal of identifying novel diagnostic and prognostic biomarkers, thus leading towards more effective targeted treatments. Following the previous annual reviews of this series, we will hereby provide a critical digest of the recent literature on small- and large-vessel systemic vasculitis, with a specific focus on novel possible disease-related biomarkers and their impact on current and future therapies.

Usefulness of antineutrophil cytoplasmic autoantibodies in diagnosing and managing systemic vasculitis.

PURPOSE OF REVIEW: Antineutrophil cytoplasmic autoantibodies (ANCAs) are considered important diagnostic tests in the work-up of patients suspected of vasculitis. Here we discuss new developments in the methodology of testing, the pitfalls in using these tests as diagnostic tools, and the value of serial ANCA testing for the follow-up of patients with ANCA-associated vasculitis including treatment decisions. RECENT FINDINGS: Both the indirect immunofluorescence (IIF) test and antigen-specific assays should be performed. New methodologies include automated reading in the IIF test and third-generation assays (anchor ELISA and bead-based multiplex assay) for the antigenic-specific assays. ANCA testing should be done in the right clinical context as positive results for PR3-ANCA and MPO-ANCA do occur in other conditions than vasculitis as well. These ANCAs develop in about 10% of patients with infective endocarditis. The occurrence of drug-induced ANCA and ANCA, also directed against elastase, following use of levamisole-adulterated cocaine should be recognized. In the right clinical context, ANCA are highly sensitive and specific for their associated disease. The value of serial ANCA testing for the follow-up of patients with ANCA-associated vasculitis is still under discussion but may be relevant in patients with renal involvement and in patients treated with rituximab. SUMMARY: The techniques for ANCA testing improve further but new tests should be standardized and validated. Their diagnostic value in the right clinical context is undisputed. Their value for the follow-up of patients is still under discussion.

Impaired function of endothelial progenitor cells in children with primary systemic vasculitis.

INTRODUCTION: Previously, we demonstrated that children with active systemic vasculitis (SV) have higher circulating CD34 + CD133 + KDR+ endothelial progenitor cells (EPC); the function of these EPCs, and their relationship with disease activity in vasculitis remains largely unexplored. We hypothesized that although EPC numbers are higher, EPC function is impaired in active SV of the young. The aims of this study were therefore to: 1. investigate the relationship between disease activity and EPC function in children with SV; and 2. study the influence of systemic inflammation on EPC function by investigating the effects of hyperthermia and TNF-α on EPC function. METHODS: We performed a cross-sectional study of unselected children with SV with different levels of disease activity attending a single center (Great Ormond Street Hospital, London) between October 2008 and December 2014. EPCs were isolated from peripheral blood of children with SV, and healthy child controls. EPC function was assessed by their potential to form colonies (EPC-CFU), and ability to form clusters and incorporate into human umbilical vein endothelial cell (HUVEC) vascular structures in matrigel. The effects of hyperthermia and TNF-α on EPC function were also studied. RESULTS: Twenty children, median age 12-years (5-16.5; nine males) were studied. EPC-CFU and the number of EPC clusters formed on matrigel were significantly reduced in children with active vasculitis compared with healthy controls (p = 0.02 for EPC-CFU; p = 0.01 for EPC cluster formation). Those with active vasculitis had lower EPC-CFU and EPC cluster formation than those with inactive disease, although non-significantly so. In addition, EPC incorporation into matrigel HUVEC networks was lower in children with SV compared with healthy children, irrespective of disease activity. Ex-vivo pre-treatment of EPC with hyperthermia impaired EPC function; TNF-α down-regulated EPC expression of CD18/CD11b and resulted in decreased incorporation into HUVEC networks. CONCLUSIONS: Whilst our previous work showed that circulating CD34 + EPC numbers are well preserved, this study revealed that EPC function is significantly impaired in children with vasculitis. It is possible that the chronic inflammatory milieu associated with vasculitis may impair EPC function, and thus contribute to an unfavourable balance between endothelial injury and repair. The mechanism of this remains to be established, however.

New insights on biomarkers in systemic vasculitis.

The systemic vasculitis is a heterogeneous group of diseases characterized by the inflammation of blood vessels. The development of advanced diagnostic tests and genetic studies have resulted in greater improvement in our understanding of vasculitis pathogenesis and thus in the development of newer therapies. However, there is still an unmet need in the management of systemic vasculitis, focused on developing of new biomarkers that would enable distinction between active disease from damage or infection and predict treatment response and prognosis.

Systemic vasculitis in a patient with rhupus syndrome.

Rhupus is a rare syndrome characterized by overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Previous reports mentioned that rhupus patients have prominent RA associated clinical manifestations and only mild organic damage related to SLE. Progressive or life-threatening manifestations are rare in rhupus patients. Our patient diagnosed as rhupus was a young women, presented with multi-organ involvement of systemic vasculitis. Rheumatologists should be aware of possibility that rhupus may be accompanied by progressive or life-threatening conditions such as vasculitis.

Red blood cell distribution width as a useful indicator to predict systemic vasculitis in patients with cutaneous vasculitis.

Cutaneous vasculitis can be limited to skin or a manifestation of primary systemic vasculitis. However, there are no definite markers to predict systemic involvements. Recent studies have shown that a higher red blood cell distribution width (RDW) is associated with disease activity in various disorders. We evaluated whether RDW can be used as an indicator for predicting systemic disease in patients with initial cutaneous involvements. We reviewed clinical and laboratory information of 143 patients with cutaneous vasculitis and 15 pigmented purpuric dermatosis patients seen at single academic hospital in Korea. Various parameters, including RDW, were evaluated in patients with primary cutaneous vasculitis and primary systemic vasculitis with initial cutaneous manifestations. The RDW value between cutaneous and systemic vasculitis patients was compared and RDW level was also investigated whether it can indicate systemic vasculitis in patients with cutaneous involvements. The mean age was 32.0 years, and 102 (64.6 %) patients were female. A total of 132 patients were patients with primary cutaneous vasculitis, and 11 were primary systemic vasculitis. Higher ratio of patients with high RDW was detected in systemic vasculitis group compared with cutaneous vasculitis group (36.4 vs. 7.6 %, P < 0.05). The mean RDW was significantly higher in systemic vasculitis patients (P < 0.05). RDW had the strongest association with systemic vasculitis (P < 0.05, OR 1.834). In conclusion, elevated level of RDW was significantly associated with systemic vasculitis. RDW can be used as one of the marker to predict systemic disease in patients with cutaneous vasculitis.

Plasma nitrite is an indicator of acute changes in ambient air pollutant concentrations.

CONTEXT: Endothelial dysfunction has been suggested as a potential mechanism by which ambient air pollution may cause acute cardiovascular events. Recently, plasma nitrite has been developed as a marker of endothelial dysfunction. OBJECTIVES: We examined the changes in plasma nitrite concentration associated with increases in ambient air pollutant concentrations in the previous 7 d. MATERIALS AND METHODS: We linked up to three measurements of plasma nitrite concentrations obtained from 49 students to 24-h average concentrations of five criteria air pollutants [particle mass < 2.5 µm in aerodynamic diameter (PM(2.5)), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3)] measured at two monitoring sites closest to Rutgers University campus (6-15 miles) in New Jersey during the years 2006-2009. We examined the change in plasma nitrite associated with each interquartile-range (IQR) increase in pollutant concentration in the previous 24 h and six preceding 24- h periods, using linear mixed models. RESULTS: IQR increases in mean PM(2.5) (7.0 µg/m³) and CO (161.7 parts per billion) concentrations in the first 24 h before the plasma nitrite measurement were associated with increased plasma nitrite concentrations (PM(2.5): 15.5 nanomolar; 95% confidence interval (CI): 2.4, 28.5; CO: 15.6 nanomolar; 95% CI: 2.4, 28.9). Increased plasma nitrite associated with IQR increases in O3 and SO2 concentrations over longer lags were observed. DISCUSSION AND CONCLUSION: Rapid increases in plasma nitrite following exposure to ambient air pollutants support the hypothesis that ambient air pollution is associated with inducible nitric oxide synthase-mediated systemic inflammation in humans.

Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarization.

Anti-neutrophil cytoplasmic antibody associated vasculitides (AAV) are conditions defined by an autoimmune small vessel inflammation. Dying neutrophils are found around the inflamed vessels and the balance between infiltrating neutrophils and macrophages is important to prevent autoimmunity. Here we investigate how sera from AAV patients may regulate macrophage polarization and function. Macrophages from healthy individuals were differentiated into M0, M1, M2a, M2b or M2c macrophages using a standardized protocol, and phenotyped according to their expression surface markers and cytokine production. These phenotypes were compared with those of macrophages stimulated with serum from AAV patients or healthy controls. While the healthy control sera induced a M0 macrophage, AAV serum promoted polarization towards the M2c subtype. No sera induced M1, M2a or M2b macrophages. The M2c subtype showed increased phagocytosis capacity compared with the other subtypes. The M2c polarization found in AAV is consistent with previous reports of increased levels of M2c-associated cytokines.

Systemic vascular inflammation in abdominal aortic aneurysm patients: a contrast-enhanced PET/CT study.

AIM: The aim of this paper was to investigate the presence of systemic vascular inflammation and its relationship with risk factors and biomarkers of systemic inflammation related to atherosclerosis in asymptomatic abdominal aortic aneurysm (AAA) patients. METHODS: Thirty AAA patients and 30 age-matched controls underwent contrast-enhanced 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET/CT. C-reactive protein, erythrocyte sedimentation rate, white blood cell count and differential, serum fibrinogen, D-dimer and full lipid panel were also evaluated. Region of interest analyses were performed to obtain target-to-background (TBR) metabolism of aorta, subclavian, carotid, iliac arteries and AAA. CT-based arterial calcium load (CL) was evaluated. Arterial Metabolism and CL intergroup differences were tested (unpaired t-test). Linear regression analysis was performed only between blood biomarkers on one side and both TBR and ACL of the arterial districts that resulted significantly different between patients and controls on the other. In all the analyses P values <0.05 were considered significant. RESULT: FDG-uptake was higher with respect to controls in aorta, carotid and iliac arteries (P<0.01, P<0.007, P<0.04 respectively). AAA and aorta metabolism showed an inverse correlation with HDL-chol (P<0.02 and P<0.01, respectively) while only aorta showed a direct correlation with lymphocytes' count (P<0.02). Carotid metabolism was directly correlated with monocytes' count and C-reactive protein concentration (P<0.02 and P<0.004, respectively). CONCLUSION: The present findings support the relevance of systemic vascular inflammation in all phases of atherosclerosis-related disorders. Moreover they confirm the concept that acute ischemic syndromes might represent the local result of a systemic inflammation rather than the focal involvement of a single arterial lesion.

Acute dilated cardiomyopathy in a patient with beriberi and cryoglobulinaemic vasculitis: an unusual potential complication of two rare disorders.

We report the case of a 45-year-old patient who presented with acute dilated cardiomyopathy. During admission the patient was consecutively diagnosed with cryoglobulinaemic vasculitis and beriberi. In both diseases, cardiac involvement may occur as dilated cardiomyopathy. Thiamin deficiency was the final cause for the severe cardiac manifestations (cardiac acute beriberi or Shoshin syndrome), which returned to normal after thiamin supplementation.

Increased serum levels of soluble vascular endothelial-cadherin in patients with systemic vasculitis.

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis (SV) in childhood characterized by an inflammatory reaction directed at vessels. Endothelial damage and perivascular leukocyte infiltrates are vital in the development of HSP. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule, which plays critical roles in angiogenesis and endothelial integrity. Herein, we investigated the serum levels of soluble VE-cadherin (sVE-cadherin) in patients with HSP and other forms of SV. The serum levels of sVE-cadherin in 30 patients with HSP, together with patients with urticarial vasculitis, allergic vasculitis, Behcet disease, psoriasis vulgaris (PV) and atopic dermatitis (AD) and 26 health controls were measured by enzyme-linked immunosorbent assay. Serum levels of sVE-cadherin were significantly increased in patients with HSP in acute stage and patients with other forms of SV but not in patients with PV or AD. Moreover, Serum sVE-cadherin levels in HSP patients were correlated with the severity of this disease and serum concentrations of IgA anticardiolipin antibodies and vascular endothelial growth factor. Taken together, we show firstly that serum sVE-cadherin is abnormally increased in HSP patients. Increased serum levels of sVE-cadherin might be a novel biomarker for evaluating the severity of HSP and useful for identifying the presence of SV in inflammatory skin conditions.

The relationship between high-sensitivity CRP and polyclonal free light chains as markers of inflammation in chronic disease.

INTRODUCTION: Serum concentrations of polyclonal free light chains (FLC) represent the activity of the adaptive immune system. This study assessed the relationship between polyclonal FLC and the established marker of innate immunity, C-reactive protein (CRP), in chronic and acute disease. METHODS: We utilized four cross-sectional chronic disease patient cohorts: chronic kidney disease (CKD), diabetes, vasculitis and kidney transplantation; and a longitudinal intensive care case series to assess the kinetics of production in acute disease. RESULTS: There was a weak association between polyclonal FLC and high-sensitivity CRP (hs-CRP) in the study cohorts. A longitudinal assessment in acute disease showed a gradual increase in FLC concentrations over time, often when CRP levels were falling, demonstrating clear differences in the response kinetics of CRP and FLC in this setting. CONCLUSION: Polyclonal FLC and hs-CRP provide independent information as to inflammatory status. Prospective studies are now required to assess the utility of hs-CRP and polyclonal FLC in combination for risk stratification in disease populations.

ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review.

Minocycline is a synthetic tetracycline-derived antibiotic with significant anti-inflammatory properties that may benefit patients with rheumatoid arthritis. Surprisingly, chronic exposure to minocycline can also cause a breach in immunologic tolerance resulting in a variety of autoimmune syndromes such as drug-induced lupus or autoimmune hepatitis. Vasculitis, most commonly resembling cutaneous polyarteritis nodosa, has also been seen in patients taking this drug. Herein, we present a case of biopsy-proven systemic vasculitis presenting as an ANA (+) ANCA (+) polyarteritis nodosa-like syndrome in a male patient who was taking minocycline for his acne for approximately 2 years. Patient initially presented with constitutional symptoms such as profound weight loss and fatigue, along with myalgias, oligoarticular arthritis, and livedo reticularis. About 2 months later, he developed a severe left testicular pain. Biopsy showed vasculitis complicated with the infarction of the left testis. Angiography revealed microaneurysms in the renal and splenic circulation. Stopping the offending drug, along with the short course of prednisone and hydroxychloroquine, resulted in prompt resolution of his symptoms. We additionally present a comprehensive review of biopsy-proven cases of vasculitis associated with chronic minocycline treatment focusing on its pathogenesis and clinical manifestations.