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Anjali Shetty,1 Rebekah Hanson,1 Peter Korsten,2 Munir Shawagfeh,3 Shiva Arami,1 Suncica Volkov,1 Olga Vila1 William Swedler,1 Abdel Naser Shunaigat,4 Sameer Smadi,4 Ray Sawaqed,5 David Perkins,1 Shiva Shahrara,1 Nadera J Sweiss11Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany; 3Anesthesia and Pain Management, King Hussein Cancer Center, Amman, Jordan; 4Liver Transplant, Kidney Transplant Royal Medical Services, Jordan; 5Cardiac Surgery Methodist Hospitals, Merrillville, IN, USAAbstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.Keywords: tocilizumab, IL-6, rheumatoid arthritis, biologics

Objective: Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models., Methods: Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis., Results: We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency., Conclusions: We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: Levels of Toll-like receptor 7 (TLR-7) are elevated in rheumatoid arthritis (RA), but the impact on RA is unknown because the endogenous ligand for TLR-7 has not been identified. The aim of this study was to identify a TLR-7 endogenous ligand and to determine its role in the pathogenesis of RA., Methods: The presence of an endogenous TLR-7 ligand, microRNA let-7b (miR-let-7b), was examined by real-time polymerase chain reaction (PCR) analysis. Using RA knockdown cells, TLR-7-knockout mice, or antagonist, the specificity of miR-let-7b as a potential ligand for TLR-7 was tested. The mechanism by which ligation of miR-let-7b to TLR-7 promotes disease was investigated in RA myeloid cells by real-time PCR, enzyme-linked immunosorbent assay, and fluorescence-activated cell sorting. We also established the effect of ectopic miR-let-7b expression on arthritic joint inflammation., Results: We found that a TLR-7 endogenous ligand resides mainly in RA synovial fluid macrophages. The GU-rich domain in miR-let-7b was found to be essential for TLR-7 ligation, since miR-147, the positive control for GU, was able to stimulate TLR-7+ myeloid cells, whereas miR-124, the negative, non-GU, control, was not. We demonstrated that miR-let-7b or exosomes containing miR-let-7b could transform the RA and/or mouse naive or antiinflammatory macrophages into inflammatory M1 macrophages via TLR-7 ligation. Consistently, we showed that miR-let-7b provokes arthritis by remodeling naive myeloid cells into M1 macrophages via TLR-7 ligation, since joint swelling and M1 macrophages are absent in TLR-7-deficient mice., Conclusion: The results of this study underscore the importance of miR-let-7b ligation to TLR-7 in the joint during the effector phase of RA., (© 2016, American College of Rheumatology.)

Objective: This study was conducted to determine the expression pattern, regulation and function of CCL28 and CCR10 in rheumatoid arthritis (RA) pathogenesis., Methods: Expression of CCL28 and CCR10 was assessed in RA compared with other arthritis synovial tissues (STs) or fluids (SFs) by histology or ELISA. The factors modulating CCL28 and CCR10 expression were identified in RA myeloid and endothelial cells by ELISA, FACS and Western blotting. The mechanism by which CCL28 ligation promotes RA angiogenesis was examined in control and CCR10-knockdown endothelial cell chemotaxis and capillary formation., Results: CCL28 and/or CCR10 expression levels were accentuated in STs and SFs of patients with joint disease compared with normal controls and they were predominately coexpressed in RA myeloid and endothelial cells. We show that protein expression of CCL28 and CCR10 was modulated by tumour necrosis factor (TNF)-α and toll-like receptor 4 ligation in RA monocytes and endothelial cells and by interleukin (IL)-6 stimulation in RA macrophages. Neutralisation of CCL28 in RA SF or blockade of CCR10 on human endothelial progenitor cells (EPCs) significantly reduced SF-induced endothelial migration and capillary formation, demonstrating that ligation of joint CCL28 to endothelial CCR10+ cells is involved in RA angiogenesis. We discovered that angiogenesis driven by ligation of CCL28 to CCR10 is linked to the extracellular signal regulated kinase (ERK) cascade, as CCR10-knockdown cells exhibit dysfunctional CCL28-induced ERK signalling, chemotaxis and capillary formation., Conclusions: The overexpression of CCL28 and CCR10 in RA ST and their contribution to EPC migration into RA joints support the CCL28/CCR10 cascade as a potential therapeutic target for RA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Our aim was to examine the impact of TLR5 ligation in rheumatoid arthritis (RA) and experimental arthritis pathology. Studies were conducted to investigate the role of TLR5 ligation on RA and mouse myeloid cell chemotaxis or osteoclast formation, and in addition, to uncover the significance of TNF-α function in TLR5-mediated pathogenesis. Next, the in vivo mechanism of action was determined in collagen-induced arthritis (CIA) and local joint TLR5 ligation models. Last, to evaluate the importance of TLR5 function in RA, we used anti-TLR5 Ab therapy in CIA mice. We show that TLR5 agonist, flagellin, can promote monocyte infiltration and osteoclast maturation directly through myeloid TLR5 ligation and indirectly via TNF-α production from RA and mouse cells. These two identified TLR5 functions are potentiated by TNF-α, because inhibition of both pathways can more strongly impair RA synovial fluid-driven monocyte migration and osteoclast differentiation compared with each factor alone. In preclinical studies, flagellin postonset treatment in CIA and local TLR5 ligation in vivo provoke homing and osteoclastic development of myeloid cells, which are associated with the TNF-α cascade. Conversely, CIA joint inflammation and bone erosion are alleviated when TLR5 function is blocked. We found that TLR5 and TNF-α pathways are interconnected, because TNF-α is produced by TLR5 ligation in RA myeloid cells, and anti-TNF-α therapy can markedly suppress TLR5 expression in RA monocytes. Our novel findings demonstrate that a direct and an indirect mechanism are involved in TLR5-driven RA inflammation and bone destruction., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Objective: To examine the impact of Toll-like receptor 5 (TLR-5) on endothelial cell function in rheumatoid arthritis (RA) and vascularization in collagen-induced arthritis (CIA)., Methods: Endothelial cell migration and tube formation assays were used to demonstrate the direct role of TLR-5 ligation in angiogenesis. Mice with CIA were treated with the TLR-5 agonist flagellin to document the effect of TLR-5 ligation in RA pathology. Vascularization in CIA was determined by immunohistochemical analysis and determination of cytokine levels in ankle joints. Spleen Th17 cells and joint interleukin-17 (IL-17) were quantified by fluorescence-activated cell sorting analysis and enzyme-linked immunosorbent assay. The development of Th17 cells induced by TLR-5 ligation was validated in RA peripheral blood mononuclear cells., Results: Ligation of TLR-5 to endogenous ligands expressed in RA synovial fluid contributed to endothelial cell infiltration and tube formation. Furthermore, treatment with flagellin after the onset of CIA exacerbated joint inflammation; in contrast, inflammation in control mice remained at a plateau phase. We showed that TLR-5-enhanced disease severity was attributable to Th17 cell differentiation and joint vascularization in CIA. Examination of the underlying mechanism using RA peripheral blood mononuclear cells documented that ligation of TLR-5 in myeloid cells and production of Th17-promoting cytokines were necessary for Th17 cell polarization. Additionally, we demonstrated that blockade of the IL-17 cascade markedly reduced endothelial cell migration activated by flagellin-conditioned medium, suggesting that TLR-5 ligation can mediate RA angiogenesis either directly by attracting endothelial cells or indirectly by fostering Th17 cell development., Conclusion: Our data demonstrate a novel role for TLR-5 in RA angiogenesis; thus, TLR-5 may be a promising new target for RA treatment., (Copyright © 2013 by the American College of Rheumatology.)

Although the role of IL-7 and IL-7R has been implicated in the pathogenesis of rheumatoid arthritis (RA), the majority of the studies have focused on the effect of IL-7/IL-7R in T cell development and function. Our novel data, however, document that patients with RA and greater disease activity have higher levels of IL-7, IL-7R, and TNF-α in RA monocytes, suggesting a feedback regulation between IL-7/IL-7R and TNF-α cascades in myeloid cells that is linked to chronic disease progression. Investigations into the involved mechanism showed that IL-7 is a novel and potent chemoattractant that attracts IL-7R(+) monocytes through activation of the PI3K/AKT1 and ERK pathways at similar concentrations of IL-7 detected in RA synovial fluid. To determine whether ligation of IL-7 to IL-7R is a potential target for RA treatment and to identify their mechanism of action, collagen-induced arthritis (CIA) was therapeutically treated with anti-IL-7 Ab or IgG control. Anti-IL-7 Ab treatment significantly reduces CIA monocyte recruitment and osteoclast differentiation as well as potent joint monocyte chemoattractants and bone erosion markers, suggesting that both direct and indirect pathways might contribute to the observed effect. We also demonstrate that reduction in joint MIP-2 levels is responsible for suppressed vascularization detected in mice treated with anti-IL-7 Ab compared with the control group. To our knowledge, we show for the first time that expression of IL-7/IL-7R in myeloid cells is strongly correlated with RA disease activity and that ligation of IL-7 to IL-7R contributes to monocyte homing, differentiation of osteoclasts, and vascularization in the CIA effector phase.

The innate immune system plays an important role in rheumatoid arthritis (RA) pathogenesis. Previous studies support the role of TLR2 and 4 in RA and experimental arthritis models; however, the regulation and pathogenic effect of TLR5 is undefined in RA. In this study, we show that TLR5 is elevated in RA and osteoarthritis ST lining and sublining macrophages and endothelial cells compared with normal individuals. Furthermore, expression of TLR5 is elevated in RA synovial fluid macrophages and RA peripheral blood monocytes compared with RA and normal peripheral blood in vitro-differentiated macrophages. We also found that TLR5 on RA monocytes is an important modulator of TNF-α in RA synovial fluid and that TLR5 expression on these cells strongly correlates with RA disease activity and TNF-α levels. Interestingly, TNF-α has a feedback regulation with TLR5 expression in RA monocytes, whereas expression of this receptor is regulated by IL-17 and IL-8 in RA macrophages and fibroblasts. We show that RA monocytes and macrophages are more responsive to TLR5 ligation compared with fibroblasts despite the proinflammatory response being mediated through the same signaling pathways in macrophages and fibroblasts. In conclusion, we document the potential role of TLR5 ligation in modulating transcription of TNF-α from RA synovial fluid and the strong correlation of TLR5 and TNF-α with each other and with disease activity score in RA monocytes. Our results suggest that expression of TLR5 may be a predictor for RA disease progression and that targeting TLR5 may suppress RA.

The association of Neisseria meningitidis infection and systemic lupus erythematosus (SLE) is uncommon. We describe here three patients with SLE who developed disseminated meningococcal disease. Each patient had long-standing SLE and was receiving treatment with prednisone. Furthermore, each patient showed serum hypocomplementemia at the time of the infection. N. meningitidis Group Y, considered to be an organism of relatively low virulence, was isolated from the blood or cerebrospinal fluid in each case. The patients presented with diverse clinical manifestations of meningococcal disease. The relationship of disseminated meningococcal infections to hypocomplementemia in patients with SLE is discussed in light of a review of the literature.

Objective: To determine the isotype specificity and clinical utility of routine testing by ELISA of IgM, IgG, and IgA rheumatoid factors (RF)., Methods: The test was performed on 619 individual specimens: blood bank donors (n = 130); rheumatoid arthritis (RA, n = 139); connective tissue diseases (CTD, n = 71); miscellaneous rheumatic disorders (MRD, n = 91); and 188 consecutive clinical laboratory specimens that tested positive by latex agglutination. Rabbit IgG was used as the antigen attached to the solid phase, and rabbit IgG antibody-enzyme conjugates against IgM (Fc5mu), IgG[F(ab')2], and IgA (alpha chain) were used, respectively, to detect IgM, IgG, and IgA RF. The serum was digested with pepsin to facilitate the measurement of IgG RF., Results: All 3 isotypes were specifically identified; IgM RF was destroyed by pepsin and IgG RF was specifically measured, without interference from IgA RF. Using data obtained from 98 RA specimens and 162 disease controls, the 3 main clinical variables--sensitivity, specificity, and predictive value--were stratified according to 3 combinations of RF isotypes: IgM only (91, 76, and 62%); IgM+IgA (79, 89, and 80%), and IgM+IgG+IgA (53, 99, and 96%). For patients with the 3 isotypes plus > 150 U of IgM and/or IgA the clinical variables were 70, 97, and 93%. In patients with RA the IgG RF was found only in association with IgM RF, i.e., there was no "hidden" RF, and IgA RF was always accompanied by IgM RF. There was a continuous decline in all 3 RF isotypes during treatment with gold salts. The sensitivity of ELISA for IgM RF exceeded that of nephelometry or latex agglutination., Conclusion: Routine measurement of IgM, IgG, and IgA RF by ELISA with rabbit IgG as the antigen and pepsin digestion for the detection of IgG RF provides useful information in the differential diagnosis of patients with arthritis.

Background: Upper airway inflammation is present in patients with obstructive sleep apnea (OSA)., Objective: To determine whether exhaled pentane and nitric oxide (NO) levels, two nonspecific markers of inflammation, are increased in patients with OSA., Methods: Exhaled nasal and oral pentane and NO levels were determined before and after sleep in 20 patients with OSA (apnea-hypopnea index, 48+/-7; mean+/-SEM) and eight healthy control subjects., Results: In patients with OSA, exhaled nasal and oral pentane levels after sleep were significantly higher than presleep values (6.1+/-1.2 nM vs 3.4+/-0.4 nM, and 7.0+/-1.3 nM vs 4.2+/-0.4 nM, respectively; p<0.05). Likewise, exhaled nasal and oral NO levels after sleep were significantly higher than presleep values in patients with OSA (39.7+/-3.8 ppb vs 28.4+/-2.9 ppb and 10.9+/-1.5 ppb vs 6.6+/-0.8 ppb, respectively; p<0.05). By contrast, there were no significant differences in exhaled nasal and oral pentane, and nasal NO levels before and after sleep in control subjects. Exhaled oral NO levels were significantly increased after sleep in comparison to presleep values in control subjects (p<0.05)., Conclusion: Exhaled nasal pentane and NO levels are increased after sleep in patients with moderate-severe OSA. These data suggest that upper airway inflammation is present in these patients after sleep.

Background: Exhaled pentane, a product of lipid peroxidation, has been proposed as an objective, nonspecific, and noninvasive marker of active inflammation. Reactive oxygen species, which elicit lipid peroxidation, are increased in asthma and contribute to airway dysfunction., Objective: To determine whether exhaled pentane levels are increased in acute asthma, and whether they decrease once acute asthma subsides., Methods: Expired air was collected through a mouthpiece into a pentane-impermeable collection bag from 12 patients (40+/-5 years; mean+/-SEM) presenting to the emergency department of the University of Illinois Hospital in Chicago with acute asthma. Exhaled air was also collected after discharge from the hospital once acute asthma subsided. Eleven patients with stable asthma (40+/-5 years) and 17 healthy volunteers (31+/-5 years) served as control subjects. Exhaled air and ambient room air were analyzed for pentane content by gas chromatography. Peak expiratory flow rates were determined in each subject., Results: Peak expiratory flow rates were 202+/-29 L/min during acute asthma and 327+/-26 L/min once acute asthma subsided (p<0.05). Exhaled pentane levels were 8.4+/-2.9 nmol/L during acute asthma and decreased significantly to 3.5+/-0.5 nmol/L once acute asthma subsided (p<0.05). Exhaled pentane levels were similar in patients with stable asthma and normal control subjects (3.6+/-0.4 nmol/L and 2.6+/-0.2 nmol/L, respectively; p>0.05). No pentane was detected in ambient air., Conclusion: Exhaled pentane levels are increased in patients with acute asthma and decrease significantly once acute asthma subsides.

Background: This study was undertaken to determine the influence of single intra-articular or intra muscular injections of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis., Patients and Methods: Twenty-one patients with rheumatic disease who had never been treated with systemic glucocorticoids and had not received local injections of these agents for the preceding 2 months, were given 40 mg of methylprednisolone acetate. Group I (11 patients) received one intra-articular injection into the knee, and Group II (10 patients) received the same dose intramuscularly., Results: In Group I, serum cortisol levels were significantly decreased 24 hours after injection (228.2 +/- 8.7 nmol/L versus 193 +/- 16.3 nmol/L; P < 0.05). Serum cortisol levels were decreased in 9 of the 11 patients, by an average of 21.5%. Two patients' levels were below 138 nmol/L, which is considered to be the lower limit of normal range. Serum cortisol levels were below normal range in 3 patients 72 hours after intra-articular steroid injection. In Group II, serum cortisol levels were significantly decreased at 72 hours after injection (239.6 +/- 10.3 nmol/L versus 175.6 +/- 21.4 nmol/L; P < 0.01). Three patients' levels were below normal. By 72 hours postinjection, serum cortisol concentrations in 9 of 10 patients were decreased by an average of 31% compared to preinjection values., Conclusion: The present study suggests that decreased adrenocortical secretion, as reflected in depressed cortisol levels, can result from a single, low-dose, intra-articular or intramuscular injection of depot corticosteroids.

Myasthenia gravis is an autoimmune disease that is associated with antibodies to acetylcholine receptors. It is associated with other autoimmune diseases such as thyroiditis (10%), systemic lupus erythematosus (2-8%), rheumatoid arthritis (4-7%), Sjögren's syndrome and polymyositis. It is not commonly found with scleroderma. We describe a case of scleroderma developing in a patient 6 years after the onset of myasthenia gravis. HLA-B8/DR3 may play a role in the association of the 2 conditions.

Objective: Systemic lupus erythematosus (SLE) is associated with lymphoproliferative diseases such as Hodgkin's lymphoma. Since there is considerable overlap between the features of SLE and Hodgkin's lymphoma (SLE/HL) there can be a great difficulty in diagnosing Hodgkin's lymphoma in the presence of SLE. Our objective was to determine the features that can suggest coexistent SLE/HL:, Methods: We describe 3 cases of Hodgkin's lymphoma that occurred in the setting of SLE and review the features of 11 reported cases in which the diseases occurred simultaneously. We compare the features of these cases with those of Hodgkin's lymphoma and SLE occurring alone., Results: Mediastinal adenopathy was seen in 58% and retroperitoneal adenopathy in 17% of patients with SLE/HL, while it was seen only rarely in these sites in cases with SLE. Severe generalized pruritus, which occurs in only 2.8% of cases of SLE, was seen in 63% of cases with SLE/HL: Features such as fever, weight loss, peripheral lymphadenopathy, splenomegaly and hepatomegaly are common to both Hodgkin's lymphoma and SLE. Renal disease is seen in half of the cases of SLE. It is rare in Hodgkin's lymphoma where, unlike SLE, it is only of minimal change or membranous type. Arthritis and positive antinuclear antibodies are rare in Hodgkin's lymphoma., Conclusions: Persistent lymphadenopathy, especially mediastinal and/or retroperitoneal lymphadenopathy, eosinophilia and generalized pruritus in a patient with SLE not responding to treatment may be indicative of coexistent Hodgkin's lymphoma.

Antibodies against very low-density lipoproteins and low-density lipoproteins (aLA) were found in 26 of 69 (38%) patients with active rheumatoid arthritis (RA) but not in any control subjects (ie, 40 patients with psoriatic arthritis, 21 patients with osteoarthritis, and 65 healthy blood donors). In 21 RA patients (30%), lipoproteins were found in the dissociated components of circulating immune complexes. RA patients with aLA had significantly decreased cholesterol levels in all lipoprotein fractions and total serum lipids, while serum triglycerides were significantly increased compared with RA patients without aLA. Anticardiolipin antibodies as measured by the Venereal Disease Research Laboratory test were not found in any subject in this study. These findings suggest a possible autoimmune origin of dyslipoproteinemia in some patients with active RA.

Purpose: Quantitative determination of breath pentane, an alkane generated by peroxidation of cellular fatty acids, has been used as a noninvasive determinant of inflammation. Herein we report the first examination of the relationship between breath pentane and intestinal inflammation in humans., Methods: Patients (N = 33), either with a known history of inflammatory bowel disease (IBD) with symptoms of relapse or with no known history of but having symptoms consistent with IBD, were evaluated with indium-111-labeled leukocyte imaging to assess the presence of active inflammation. At the time of the indium scan, the exhaled breath of the patients was obtained via a collecting tube. Gas chromatography was used to quantify the pentane content, and these values were compared with graded indium scans., Results: The range of breath pentane found in our population (36 determinations in 33 patients) was from 0 to 38.4 nmol/l of exhaled air. For patients with negative scans, the mean pentane was 2.1 nmol/l, for intermediate scans 3.1, for positive scans 4.3, and for nonintestinal nuclide imaging 5.5 [P = 0.005 by analysis of variance (ANOVA)]., Conclusions: We have previously demonstrated the correlation of breath pentane with gross and histologic evidence of intestinal inflammation in a rodent colitis model. This current study also demonstrates that pentane analysis can be correlated with inflammatory bowel disease activity in humans.

Concentrations of serum lipids and serum very low-density lipoproteins and low-density lipoproteins (VLDL+LDL, originally called beta lipoproteins) were measured and agarose gel electrophoresis of serum lipoproteins was performed in 69 patients with active rheumatoid arthritis (RA), 40 patients with psoriatic arthritis (PA), 21 patients with osteoarthritis (OA), and 65 healthy blood donors. These lipid parameters were also compared in 21 RA and 40 PA patients during periods of severe disease activity (SA) versus minimal disease activity (MA). RA patients had significantly decreased concentrations of total serum lipids, total serum cholesterol, cholesterol in LDL, and cholesterol in high-density lipoproteins (HDL) compared with healthy blood donors. RA patients with SA had significantly decreased cholesterol in LDL and HDL compared with patients with MA. As the disease activity decreased, RA patients had normalization of almost all serum lipid concentrations. Electrophoresis of serum lipoproteins showed heterogeneous patterns in RA patients. Patients with PA also had some evidence of dyslipoproteinemia. Serum lipids changed with disease activity in PA patients in a manner similar to that in RA patients. These data show that patients with RA and PA have a dyslipoproteinemia that is related to disease activity.

Objective: To determine the effects of aurothioglucose, aurothiomalate, and auranofin on basal and forskolin-activated adenylyl cyclase activity in human total lymphocyte membranes, and in membranes of T and B lymphocyte subsets., Methods: Membranes were isolated from human total lymphocytes and T and B cell subsets. The effects of gold compounds on basal and forskolin-stimulated activity of adenylyl cyclase were measured by radioassay., Results: The gold compounds inhibited adenylyl cyclase activity. This inhibitory effect required the presence of both the sulfhydryl ligands and aurous cation., Conclusion: Regulation of lymphocyte adenylyl cyclase by gold compounds represents a potential mode of action of these drugs in rheumatic diseases.

We studied retrospectively the pattern of septic arthritis in childhood at a major municipal hospital during a ten-year period. Hemophilus influenzae was the most common organism in septic arthritis in patients less than two years old and was associated with upper respiratory tract infections in nine of 12 patients (75%). Staphylococcus aureus was seen in seven of eight (87.5%) children above the age of five and was associated with history of trauma. All patients were black. Despite the high incidence of sickle cell disease in our hospital population, not one patient had sickle cell disease.