The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to ...pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean ± sd 1.6 ± 1.1 versus 5.3 ± 4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.
The aim of our study was (i) to compare the clinical and biological characteristics of 148 (137 women, 11 men) primary Sjögren's syndrome (pSS) patients at diagnosis as a function of their sex and ...(ii) to assess the prognostic value of anti-calpastatin and anti-alpha-fodrin autoantibodies. In addition, the presence of anti-nuclear antibodies (ANA), anti-52- and 60-kDa Sjögren's syndrome A (SSA), anti-Sjögren's syndrome B (SSB), anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factors (RF) of IgA, IgG and IgM isotypes was sought in sera collected at pSS onset. Raynaud's syndrome, significantly more frequent in women, was the only systemic manifestation of pSS whose frequency differed significantly as a function of the patient's sex (P = 0·02). ANA (P = 0·001) and anti-60-kDa SSA autoantibodies (P = 0·03) were significantly more common in women, while men never synthesized detectable levels of anti-SSB, anti-calpastatin or IgG anti-alpha-fodrin autoantibodies. In addition, anti-CCP autoantibodies were found in low percentages of pSS patients (4% F/18% M). The absence of autoantibodies does not exclude the diagnosis of pSS in men that will be based mainly on the anatomopathological findings of a minor salivary gland biopsy. Positivity of anti-60-kDa SSA, anti-SSB, anti-calpastatin, IgA and IgG anti-alpha-fodrin antibodies is not associated with pSS clinical and biological severity.
Systemic erythematosus lupus (SLE) is a common autoimmune disease. Disease flares may mimic infection with fever, inflammatory syndrome and chills, sometimes resulting in a difficult differential ...diagnosis. Elevated serum procalcitonin (PCT) levels have been reported to be predictive of bacterial infections, but with conflicting results. The value of serum procalcitonin has not been assessed in large series of SLE. We aimed to describe the distribution of PCT levels in SLE patients with and without flares, to assess the factors associated with increased PCT levels, and to determine the positive and negative predictive values of increased PCT for bacterial infection in SLE patients. Hospitalized SLE patients were included in a retrospective study. Serum PCT had been assayed, or a serum sample had been frozen on admission, before treatment modification. Serum PCT, measured by an automated immunofluorometric assay, and SLEDAI were assessed at the same time. Some 53 women (median age: 33.7 years, range 16–76) and seven men (median age: 52.5 years ± 19) were included. The median SLEDAI for patients with flare (n = 16, 28%) was 2 (range: 0–29). Five patients (8%) had systemic infection. Only one patient had increased PCT levels. Men had significantly higher PCT levels than women (0.196 ± 0.23 versus 0.066 ± 0.03, p < 0.01) and a significant correlation was observed between PCT, age, erythrocyte sedimentation rate, and C-reactive protein. We conclude that PCT levels were within the normal range in infected and non-infected SLE patients and there was no ability to differentiate SLE patients with or without bacterial infection.
Objective
Findings from the WEGENT trial and other short‐term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with ...polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period.
Methods
Long‐term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models.
Results
Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval 95% CI 11.3–12.5 years). In patients receiving AZA and those receiving MTX, the 10‐year overall survival rates were 75.1% (95% CI 64.8–86.9%) and 79.9% (95% CI 70.3–90.8%) (P = 0.56), respectively, and relapse‐free survival rates were 26.3% (95% CI 17.3–40.1%) and 33.5% (95% CI 23.5–47.7%) (P = 0.29), respectively. No between‐treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between‐treatment differences in survival rates were observed. The 10‐year relapse‐free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti–proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate.
Conclusion
The results of this long‐term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA‐associated vasculitides.
Excess 5-aminolevulinic acid (ALA) and α-aminoacetone (AA) are implicated in ketosis, porphyrinpathies and diabetes. Pathologic manifestations involve O2−, H2O2, OH, enoyl radicals (ALA and AA) and ...their oxidation end products.
To characterize enoyl radicals resulting from reaction of OH radicals with ALA and AA, micromolar OH concentrations were produced by pulse radiolysis of ALA and AA in aqueous solutions.
ALA and AA react with OH at k=1.5×109M−1s−1. At pH7.4, the ALA absorbance spectrum has a maximum at 330nm (ε=750M−1cm−1). This band appears as a shoulder at pH8.3 where two ALA species are present: (NH3)+-CH2-CO-CH2-CH2-COO− and NH2-CH2-CO-CH2-CH2-COO− (pKa=8.3). At pH8.3, ALA reacts with oxygen (k=1.4×108M−1s−1) but not with O2−. At pH8.3, AA oxidation produces two AA species characterized by an absorbance spectrum with maxima at 330 and 450nm. ALA and AA are repaired by antioxidants (quercetin (QH), catechin, trolox, ascorbate) which are semi-oxidized (k>108M−1s−1). QH bound to HSA or to apoferritin and ferritin repairs ALA and AA. In O2-saturated apoferritin solutions, Q, O2−, AA and reaction product(s) react with QH.
The optical absorption properties and the time evolution of ALA and AA were established for the first time. These radicals and their reaction products may be neutralized by antioxidants free in solution or bound to proteins.
Adjuvant antioxidant administration may be of interest in pathologies related to excess ALA or AA production.
•ALA and α-aminoacetone (AA) autooxidation leads to pathologic disturbances.•Enoyl radicals, O2−, H2O2, and OH are produced by this autooxidation.•ALA and AA are oxidized by OH at a rate of 1.5×109M−1s−1 with enoyl radical formation.•Enoyl radicals readily react with O2 but not with O2−.•Enoyl radicals and end products are neutralized by free or protein-bound antioxidants.
Abstract
Ferritin (Ft) impairment through *O2-, H2O2, and *OH production occurs in the cases of ketoses, diabetes mellitus, acute intermittent porphyria and tyrosinemia. In addition to *Trp and TyrO* ...radical production, ferrous iron liberation and Ft synthesis stimulation, site-specific oxidation reactions are induced leading to toxic iron accumulation in organs with high Ft content, for example, liver and brain. To elucidate the potential pathways to Ft recovery, repair of oxidative damage to horse spleen apoferritin (apoFt) and Ft by quercetin (QH) or rutin (RH) was studied in the presence and absence of oxygen. *Trp and TyrO* radicals were produced in pulse radiolysis through apoFt oxidation by *Br2- radicals. QH and RH bind to apoFt on eight sites with binding constants of ˜80,000 and ˜32,000 M−1, respectively. In deaerated solutions, a repair of apoFt radicals is observed involving both bound and free flavonoids. This repair occurs by a fast intra- and a slow inter-molecular electron transfer from bound and free flavonoids, respectively. With QH, the rate constants are 104 s-1 and 3.5 × 107 M-1 s-1 for the intra- and intermolecular repair reactions, respectively. Oxygen does not interfere with repair of apoFt or Ft by bound QH but inhibits 90% of Ft repair by RH. These results taken together indicate that flavonoid antioxidants may help alleviate Ft impairment in diseases involving an oxidative stress.
Infectious complications currently account for 80% of deaths from acute pancreatitis. The aim of this study was to evaluate the necessity for prophylactic antibiotics in patients with severe acute ...pancreatitis. Twenty-three consecutive patients suffering from acute alcoholic pancreatitis with computed tomography demonstrating two or more fluid collections were randomly assigned to one of two groups receiving either nonantibiotic treatment or prophylactic antibiotics (ceftazidime, amikacine, and metronidazole for 10 days). Sepsis was always diagnosed by positive cultures. Seven episodes of severe sepsis occurred (pancreatic infection and septic shock) in the nonantibiotic group, and no infection occurred in the prophylactic antibiotic group (p < 0.03). In conclusion, the use of prophylactic antibiotics in severe alcoholic acute pancreatitis significantly reduces the incidence of severe infection.
Permanent visual loss (PVL) is the most feared complication of giant cell arteritis (GCA), and its risk factors are still unclear.
The aim of our study was to assess the pathological features ...predictive of PVL on temporal artery biopsy (TAB) specimens in patients with GCA.
The slides of 391 TAB specimens from patients with GCA were reviewed by two pathologists without clinical information.
A total of 29 patients (26 females and 3 males, mean age 78.3 years) presented with unilateral PVL at the onset of the disease, and 362 patients (258 females, 104 males, mean age 74.7 years), did not. The pathological features strongly predictive for PVL were the presence (p = 0.003), number (p = 0.001) and aggregates of giant cells (p = 0.001), presence of plasmocytes (p = 0.002), thickened intima (p = 0.007), neoangiogenesis (p = 0.001) and degree of arterial occlusion (p = 0.006). Presence of neutrophils, eosinophils, parietal necrosis, calcification in the arterial wall and disruption of the internal elastic membrane were similar in both groups. Total obstruction of the arterial lumen by a thrombus, intensity of the inflammatory cells infiltration and inflammation of small vessels, nerves and veins surrounding the temporal artery were not associated with blindness. In multivariate analysis, only giant cells remained significantly associated with PVL.
Giant cells are strongly associated with PVL, with a significant gradient between great risk and large number of giant cells. However, PVL was neither associated with the intensity of the inflammatory infiltrate, nor with the presence of arterial thrombosis.
To evaluate vascular expression of annexin A2 (ANXA2) and its subunit S100A10 in lupus nephritis (LN).
The present histological study included 14 patients with LN and 11 controls (patients with ...non-lupus kidney diseases). Kidney biopsies from patients with lupus were scored for lupus glomerulonephritis (according to the International Society of Nephrology/Renal Pathology Society 2003 classification) and vascular lesions (such as microthrombi and antiphospholipid syndrome nephropathy (APSN)). ANXA2 and S100A10 expression in glomerular and peritubular capillaries was evaluated by immunohistochemistry on tissue sections. The staining intensity score ranged from 0 (no expression) to 4 (intense expression).
In patients with LN, the median age (range) at first kidney biopsy was 36 (18-49). Vascular lesions were observed in six patients (including two with APSN). We observed intense expression of ANXA2 in glomerular and peritubular capillaries while expression of S100A10 was weaker. However, one of the patients with APSN showed strong S100A10 expression. Patients with LN and controls differed significantly in terms of S100A10 expression in peritubular capillaries. We also observed a statistical difference between patients who had LN with renal vascular lesions and those without renal vascular lesions in terms of ANXA2 expression in peritubular capillaries.
The presence of vascular lesions in LN appears to be associated with significant differences in the vascular expression of ANXA2. Vascular expression of ANXA2 was somewhat higher in LN. Vascular expression of S100A10 was somewhat lower in LN (except one of the two patients with APSN). Further studies of ANXA2's putative value as a biomarker of active LN or of vascular lesions in LN are required.
Objectives. An epidemic pattern has been reported for GCA and PMR. Immunological studies have shown that an unknown antigen activates the dendritic cells of the adventitia and the type 4 toll-like ...receptors. Procalcitonin (PCT) is an early marker of bacterial infection. The goal of the study was to assess the level of PCT in GCA and PMR at the onset of the disease. Methods. Patients diagnosed during the 2002–06 period were randomly selected. All the 46 patients fulfilled the ACR or the Hunder criteria, and all blood samples were taken before steroid therapy. Results. PCT was normal in all patients. PCT was slightly increased in men (0.087 ± 0.023 μg/l) compared with women (0.066 ± 0.027 μg/l) (P = 0.009), and in PMR (0.092 ± 0.027μg/l) compared with GCA (0.068 ± 0.026 μg/l) (P = 0.018). There was no significant correlation with inflammation markers. Conclusions. These results are not in favour of a bacterial trigger for GCA or PMR. Increased PCT levels in patients with inflammatory syndrome, GCA–PMR symptoms and negative temporal artery biopsy may rule out the diagnosis of GCA and PMR.
PDF
