Serum soluble triggering receptor on myeloid cells-1 (sTREM-1) is elevated in systemic lupus erythematosus but does not distinguish between lupus alone and concurrent infection.

We sought to determine serum triggering receptor expressed on myeloid cell-1 (sTREM-1) level in a cohort of patients with systemic lupus erythematosus (SLE). Serum sTREM-1 level of 98 patients with SLE and 49 healthy controls was assayed by ELISA. Serum sTREM-1 level was significantly elevated in a cohort of 78 unselected consecutively recruited patients with SLE (mean 1.1 ± 2.8 ρg/ml, median 0.02 ρg/ml) compared to that of the controls (mean 0.11 ± 0.3 ρg/ml, median 0 ρg/ml; p < 0.0001). We also determined serum sTREM-1 level of 20 SLE patients with a concurrent infection (mean 0.6 ± 1.1 ρg/ml, median 0.12 ρg/ml) and found it not statistically significant compared with that of the patients without infection. Serum sTREM-1 level did not correlate with SLE disease activity. Our finding of elevated serum sTREM-1 level suggests an increased shedding of TREM-1 in SLE and a possible novel pathway of innate immune response in autoimmunity.

Monocyte chemoattractant protein-1 in the aqueous humour of patients with age-related macular degeneration.

BACKGROUND: To investigate the role of inflammation in age-related macular degeneration by measuring the levels of cytokines in the aqueous humour. METHODS: Samples of aqueous humour were collected from 34 patients with age-related macular degeneration and 16 age-matched control subjects undergoing cataract surgery. Age-related macular degeneration stage was determined clinically, before surgery. Levels of cytokines were measured using Luminex X-MAP technology, and positive results were verified by Western blot. RESULTS: Age-related macular degeneration was moderate in 18 patients and advanced in 16. The advanced age-related macular degeneration group was further divided into patients with active choroidal neovascularization (n = 7), disciform scar (n = 7) or central geographic atrophy (n = 2). Higher-than-normal levels of monocyte chemoattractant protein-1 in the aqueous humour were associated with advanced age-related macular degeneration (200 ± 140 pg/mL vs. 100 ± 61 pg/mL; P = 0.03), especially active choroidal neovascularization (255 ± 155 pg/mL; P = 0.02), Western blot analysis verified the monocyte chemoattractant protein-1 findings. Patients with disciform scar showed a trend of abnormally high levels of interleukin-12 (p70) (1.7 ± 2.4 pg/mL vs. 0.2 ± 1 pg/mL; P = 0.07), tumour necrosis factor-α (1.8 ± 2.4 pg/mL vs. 0.3 ± 1 pg/mL; P = 0.06) and interleukin-12 (4.7 ± 6.4 pg/mL vs. 1.2 ± 2.1 pg/mL; P = 0.08). CONCLUSION: Elevated levels of inflammation-related cytokines in the aqueous humour in various stages of age-related macular degeneration may suggest a pathogenic role of inflammation. Monocyte chemoattractant protein-1 may be indicative of the angiogenic phase. Further corroborative studies are required.

Increased plasma and optic nerve levels of IL-6, TNF-alpha, and MIP-2 following induction of ischemic optic neuropathy in mice.

PURPOSE: To investigate levels of proinflammatory cytokines in a mouse model of anterior ischemic optic neuropathy (rAION). METHODS: AION was induced in C57/BL6 mice and levels of IL-6, TNF-alpha, and MIP-2 were measured in plasma by ELISA and in the optic nerves by RT-PCR at predetermined intervals. RESULTS: Plasma: IL-6 levels were elevated immediately after rAION induction and decreased gradually thereafter. TNF-alpha showed an early peak on day 1 and again from day 21. MIP-2 levels were increased until day 7. Optic nerve: IL-6, TNF-alpha, and MIP-2 levels increased within a few hours and then decreased gradually. IL-6 had a second peak on day 3. CONCLUSIONS: Proinflammatory cytokines may play a role in the pathogenesis of rAION.

Antiphospholipid antibodies may be a new prognostic parameter in aggressive non-Hodgkin's lymphoma.

OBJECTIVES: Patients with malignancies have an increased prevalence of antiphospholipid antibodies (APA). The aim of this study was to determine the prevalence of IgG, IgM, and IgA anticardiolipin antibodies (aCL) and anti-beta-2 glycoprotein I antibodies (anti-beta2-GPI) in patients with non-Hodgkin's lymphoma (NHL), and to investigate their clinical and prognostic significance. METHODS: The study group included 86 patients with NHL. Enzyme-linked immunosorbent assay kits were used to measure the concentrations of aCL and anti-beta2-GPI, and coagulation tests, to measure lupus anticoagulant (LAC) activity. Blood was collected at diagnosis in all patients and at follow-up in 15. Median follow-up time was 1.9 yr. RESULTS: Elevated APA levels were found in 35 patients (41%) at diagnosis: one patient aCL IgG, five patients aCL IgM, five aCL IgA, one anti-beta2-GPI IgG, 14 anti-beta2-GPI IgM, and 19 anti-beta2-GPI IgA; LAC activity was found in three of 67 patients (4.5%). There was no significant correlation between elevated APA levels and patient's age or sex, disease stage or grade, bone marrow involvement, B symptoms, serum lactate dehydrogenase levels, serum beta2 microglobulin levels, International Prognostic Index (IPI) score, performance status, type of treatment, or response to treatment. There was a correlation between elevated APA and absence of extranodal disease (P = 0.045). A strong negative correlation was found between elevated APA at diagnosis and survival time. Two-year survival was 90 +/- 5% for patients without APA at diagnosis compared with 63 +/- 11% for patients with an elevated APA levels (P = 0.0025). APA added to the predictive value of IPI for event-free and overall survival. CONCLUSIONS: APA are elevated in 41% of NHL patients at diagnosis and are correlated with shortened survival. Their level may serve as an independent prognostic variable in aggressive NHL.

Increased prevalence of antithyroid antibodies and subclinical hypothyroidism in children with juvenile idiopathic arthritis.

OBJECTIVE: To estimate the occurrence of antithyroid antibodies (ATA) and hypothyroidism in children with juvenile idiopathic arthritis (JIA) compared to matched healthy controls. METHODS: The occurrence of ATA, including antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies, was evaluated by quantitative immunometric ELISA in children with JIA and in a healthy matched control group. Thyroid function was assessed in both groups. RESULTS: The study group included 66 patients with JIA (50 girls, 16 boys) of mean age 11.7 +/- 4.4 years (range 2-23). The control group included 89 children (71 girls, 18 boys) of mean age 10.8 +/- 4.2 years (range 2-18). Mean age at onset of joint disease was 7.3 +/- 3.6 years (range 1-15). Anti-TG antibodies were found in 7 of 62 patients (11.3%) in the JIA group and 2 of 89 controls (2.2%) (p = 0.03); anti-TPO antibodies were found in 5 of 65 patients (7.9%) and one of 89 controls (1.1%) (p = 0.08). All patients with ATA had oligoarticular type JIA (p = 0.01). Mean thyroid stimulating hormone (TSH) levels were higher in the study group than in controls (2.6 +/- 2.3 vs 1.9 +/- 1.0 mIU/l; p = 0.01); levels were above normal range (0.4-4 mIU/l) in 8 study patients (12%) and 3 controls (3.4%) (p = 0.055). Overall, ATA were found in 9 of the 150 study participants, 4 (44%) of whom had TSH levels above 4 mIU/l (p = 0.001). CONCLUSION: Children with JIA have a higher than normal incidence of ATA and subclinical hypothyroidism and should be routinely screened for these variables.

Inflammatory reaction in acute retinal artery occlusion: cytokine levels in aqueous humor and serum.

PURPOSE: To investigate the role of inflammation in acute retinal artery occlusion (RAO). METHODS: Levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) were measured in serum (n = 14) and aqueous humor (AqH) (n = 8) samples from patients with RAO. Findings were compared with 24 age- and disease-matched patients, 10 healthy subjects (serum), and 16 patients undergoing cataract surgery (AqH). RESULTS: Patients who arrived early (within 4-6 hours of occlusion) had higher serum IL-8 and IL-6 levels than controls; the IL-6 level in the AqH was lower than that of controls, while the IL-8 level was higher. In seven patients for whom both serum and AqH samples were available, serum IL-6 levels were higher than their corresponding AqH levels in most patients arriving within 10 hours of occlusion, and AqH IL-8 levels were higher than the corresponding serum levels in all but one. TNF-alpha levels were consistently higher in the serum than in the AqH at all time points. CONCLUSIONS: Serum IL-8 and IL-6 and AqH IL-8 are elevated immediately following acute RAO. The early local suppression of IL-6 may be related to ocular immune mechanisms.

Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia.

BACKGROUND AND OBJECTIVES: Conventional endoscopic and radiographic methods fail to identify a probable source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients, as well as subjects refractory to oral iron treatment, are often referred for hematologic evaluation. DESIGN AND METHODS: Patient clinic, screened for non-bleeding gastrointestinal conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H. pylori infection (IgG antibodies confirmed by urease breath test). RESULTS: The mean age of all subjects was 39+/-18 years, and 119 of 150 were females. We identified 8 new cases of adult celiac disease (5%). Forty IDA patients (27%) had autoimmune atrophic gastritis of whom 22 had low serum vitamin B12 levels. H. pylori infection was the only finding in 29 patients (19%), but was a common co-existing finding in 77 (51%) of the entire group. Refractoriness to oral iron treatment was found in 100% of patients with celiac disease, 71% with autoimmune atrophic gastritis, 68% with H. pylori infection, but only 11% of subjects with no detected underlying abnormality. H. pylori eradication in previously refractory IDA patients in combination with continued oral iron therapy resulted in a significant increase in hemoglobin from 9.4+/-1.5 (mean +/- 1SD) before, to 13.5+/-1.2 g/ dL (p<0.001 by paired t test) within 3 to 6 months. INTERPRETATION AND CONCLUSIONS: The recognition that autoimmune atrophic gastritis and H. pylori infection may have a significant role in the development of unexplained or refractory IDA in a high proportion of patients should have a strong impact on our daily practice of diagnosing and managing IDA.

Recurrent parotitis in selective IgA deficiency.

Recurrent parotitis is an uncommon condition in children. In most cases the etiology is unknown, although the disease is occasionally associated with viral infections, autoimmune disorders and immunodeficiency. We describe, for the first time, a child with recurrent parotitis and isolated immunoglobulin A (IgA) deficiency, without autoimmune disease. As IgA is the main immunoglobulin secreted into the mucosal surfaces, including that of the respiratory and gastrointestinal tracts, and into the saliva, the lack of IgA may be involved in the pathogenesis of recurrent parotitis. We recommend that IgA and other immunoglobulins be tested in all cases of recurrent parotitis.