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Objectives To compare the efficacy and safety of a new formulation of a fixed dose combination of glucosamine sulfate (GS; 1500 mg) and bovine chondroitin sulfate (CS; 1200 mg) versus the reference product (RP) in patients with knee osteoarthritis (OA). Methods In this multicenter, randomized, single-blind trial, 627 patients with knee osteoarthritis (OA)—Kellgren-Lawrence grades 2 or 3 and mean score ≥ 40 mm in the WOMAC pain subscale—were randomized to receive GS/CS or the RP for 24 weeks. The primary efficacy endpoint was the absolute change in WOMAC pain subscale score. The secondary endpoints included the following: WOMAC total and subscale scores, overall assessment of the disease by the patient and the investigator, SF-12 score, OMERACT-OARSI response rate to the treatment, and rescue medication use. Results Mean reductions of WOMAC pain score were − 35.1 (sd = 23.2) mm in the GS/CS group and − 36.5 (sd = 24.9) mm in the RP group. The difference between the adjusted means of both treatments confirmed the non-inferiority of GS/CS versus the RP. Improvement was observed in pain, stiffness, physical function and total WOMAC score, as well as in overall OA assessment by the patient and the investigator for both groups. No improvement was observed in SF-12. The rate of OMERACT-OARSI responders was 89.4% in GS/CS group and 87.9% in the RP group. Headache and changes in glucose tolerance were the most frequent treatment-related adverse events. Conclusions The new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin sulfate was non-inferior to the RP in symptomatic treatment of knee OA, with a high responder rate and good tolerability profile. Trial registration ClinicalTrials.gov; Registration number NCT02830919; Date of registration: July 13, 2016; First randomization date: December 05, 2016).

Previous studies found that physicians working in developed countries in Europe and in the USA declared insufficient knowledge concerning immune-related adverse events (irAE) following use of immune checkpoint inhibitors (ICI) in cancer treatment. We determined this knowledge gap among rheumatologists and medical students (MS) in Brazil. A web-based structured survey or a direct interview was applied to 1428 board-certified Brazilian rheumatologists and an adapted questionnaire was sent to 840 undergraduate MS attending the last 2 years of Medical Schools in Fortaleza-CE, Brazil, in September 2019. 228 (15.9%) rheumatologists and 145 (17.2%) MS answered the survey; 136 (60%) rheumatologists worked at Institutions with Oncology service. Rheumatologists had 22.6 ± 12.6 years of medical practice, most [116 (50.9%)] worked in private practice and 9 (3.9%) were on training. Fifty-three (23.4%) declared being familiar [40 (17.6%)] or very familiar [13 (5.8%)] with irAE. Almost two-thirds declared having never managed irAE and about a third (38.6%) felt confident in managing such patients. Knowledge among rheumatologists was similar regardless of having more or less than 10 years of practice (P = 0.758). Less than 5% MS declared being familiar with ICI and most have never heard of irAE. There is a large gap concerning knowledge about ICI and irAE among rheumatologists and MS in Brazil. Continuing medical education strategies are needed to improve this knowledge.

Pérola Grinberg Plapler,1 Morton Aaron Scheinberg,2 Christina da Cunha Ecclissato,3 Monalisa Fernanda Bocchi de Oliveira,3 Roberto Bleuel Amazonas31Orthopedic and Traumatology Institute of Clinical Hospital, University of São Paulo, 2Clinical Research Center Hospital AACD, São Paulo, 3NC Group Medical Affairs, Hortolândia, São Paulo, Brazil Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids.Objective: The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity.Patients and methods: In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10mg three times daily or oral NA 250mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis.Results: KT was not inferior to NA for the reduction in LBP over 5days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland–Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting.Conclusion: KT is not inferior in efficacy and delivers faster pain relief than NA.Keywords: ketorolac trometamol, naproxen, acute low back pain, nonsteroidal anti-inflammatory drugs

Morton Scheinberg,1 Henrique Pott Júnior,2 Eduardo de Almeida Macêdo,2 Monalisa Fernanda Bocchi de Oliveira,2 Christina Ecclissato,2 Roberto Bleuel Amazonas2 1Clinical Research Center Hospital AACD, Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Medical Affairs Department, EMS Pharma Inc., Hortolândia, Brazil Purpose: This study investigated the safety and efficacy of fixed-dose combination tablets of naproxen/esomeprazole magnesium and nimesulide/pantoprazole to determine if both regimens are equally suited to relieve pain in patients with osteoarticular diseases and dyspeptic symptoms. Methods: Patients were randomly assigned to receive either nimesulide/pantoprazole (100mg/20mg) twice daily or naproxen/esomeprazole magnesium (500mg/20mg) twice daily for 14 days. The primary endpoint was defined as the mean change in modified Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Secondary endpoints were mean visual analog scale score of dyspeptic symptoms (nausea, abdominal discomfort/pain, epigastric burning, postprandial fullness), mean visual analog scale score of individual dyspeptic symptoms, and individual score of dyspeptic symptoms according to patient diary. This study is registered at ClinicalTrials.gov: NCT01670552. Results: A total of 490 patients were enrolled and randomized, and 399 completed treatment (naproxen/esomeprazole, n=201; nimesulide/pantoprazole, n=198). The difference in mean change in the modified Western Ontario and McMaster Universities Osteoarthritis Index pain score after 7 days of treatment between the two treatment groups was 2.33mm (95%CI, -1.22 to 5.89mm). After 14 days of therapy, the difference was 0.45mm (95%CI, -3.29 to 4.19mm). The most common adverse events in the pooled group were abdominal discomfort, abdominal distention, dyspepsia, and nausea, but none of these was deemed to be clinically meaningful. Conclusion: The present study demonstrated noninferiority of a 14-day regimen with a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for the treatment of osteoarticular pain. Keywords: osteoarticular diseases, naproxen, esomeprazole, nimesulide, pantoprazole, randomized controlled trial

BACKGROUND: Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin ( TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2'- O-methoxyethyl-modified antisense oligonucleotide, inhibits hepatic production of transthyretin. METHODS: We conducted an international, randomized, double-blind, placebo-controlled, 15-month, phase 3 trial of inotersen in adults with stage 1 (patient is ambulatory) or stage 2 (patient is ambulatory with assistance) hereditary transthyretin amyloidosis with polyneuropathy. Patients were randomly assigned, in a 2:1 ratio, to receive weekly subcutaneous injections of inotersen (300 mg) or placebo. The primary end points were the change in the modified Neuropathy Impairment Score+7 (mNIS+7; range, -22.3 to 346.3, with higher scores indicating poorer function; minimal clinically meaningful change, 2 points) and the change in the score on the patient-reported Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating poorer quality of life). A decrease in scores indicated improvement. RESULTS: A total of 172 patients (112 in the inotersen group and 60 in the placebo group) received at least one dose of a trial regimen, and 139 (81%) completed the intervention period. Both primary efficacy assessments favored inotersen: the difference in the least-squares mean change from baseline to week 66 between the two groups (inotersen minus placebo) was -19.7 points (95% confidence interval [CI], -26.4 to -13.0; P

Immunopathological aspects of interleukin-6 are analyzed, as well as the clinical use of tocilizumab, its safety and efficacy. Several studies have demonstrated that the blockade of interleukin-6 may bring a therapeutic benefit to rheumatoid arthritis patients. Tocilizumab is a humanized monoclonal antibody against the cell and soluble receptor of interleukin-6 and it also changes the levels of vascular endothelial growth factor. Although its mechanism of action is not completely known to date various reports on medical literature show that its benefits are quite reliable and suggest that it will be a new anticitokine treatment for inflammatory arthritis.

Rituximab is a chimeric monoclonal antibody capable of depleting Bcells expressing CD20. Clinical trials carried out in patients diagnosedwith active, established RA confirm that a single cycle of rituximabgiven as two infusions a week apart, together with once weekly oralmethotrexate, produces enduring clinical responses comparable tothat observed with TNF blockade and may slow the rate of structuraldamage to joints. Rituximab, which has recently been approved for usein active rheumatoid arthritis refractory to TNF inhibitors, exhibits anacceptable safety record in rheumatoid arthritis trials, but its infusioncan be followed by reactions of variable frequency and severity which,in most instances, can be prevented by intravenous administration ofcorticosteroids and anti-histamines prior to the infusion. The long-termsafety record of rituximab as observed from the follow-up of patientstreated for non-Hodgkin’s lymphoma is favorable and reassuring.Current uncertainties regarding rituximab usage in rheumatoidarthritis are: (a) management of rituximab treatment failures, and (b)lack of reliable biomarkers to rationally indicate the best choice of thebiologic agent.

Objective: To analyze the use and results of infliximab therapy atHospital Israelita Albert Einstein (HIAE) from 2001 to 2006. Methods:Questionnaire filled by physicians who prescribed infliximab. Clinicaldata for each individual patient was provided by the attendingrheumatologist according to individual standards. The main reasonfor prescribing infliximab was failure to respond to other diseasemodifying anti-rheumatic drugs. Treatment escalation was definedas increase and/or a decrease in the interval between infusions ofinfliximab (inter-infusional interval). Results: The mean duration ofinfliximab therapy was 78 ± 54 weeks. Patients were more likely todiscontinue treatment during the first two years mainly due to noefficacy. Thirty percent of patients required dose adjustments while8% tolerated longer inter-infusional intervals. Conclusions: Thedata confirms the efficacy of infliximab in the treatment ofinflammatory arthritis. Approximately 50% of patients discontinuedthe medication and one third required dose adjustments. A smallnumber of patients tolerated inter-infusional periods wider thanthe recommended 8 weeks.

Recent data suggest that the clinical course of reactional states in leprosy is closely related to the cytokine profile released locally or systemically by the patients. In the present study, patients with erythema nodosum leprosum (ENL) were grouped according to the intensity of their clinical symptoms. Clinical and immunological aspects of ENL and the impact of these parameters on bacterial load were assessed in conjunction with patients' in vitro immune response to mycobacterial antigens. In 10 out of the 17 patients tested, BI (bacterial index) was reduced by at least 1 log from leprosy diagnosis to the onset of their first reactional episode (ENL), as compared to an expected 0.3 log reduction in the unreactional group for the same MDT (multidrug therapy) period. However, no difference in the rate of BI reduction was noted at the end of MDT among ENL and unreactional lepromatous patients. Accordingly, although TNF-alpha (tumor necrosis factor) levels were enhanced in the sera of 70.6% of the ENL patients tested, no relationship was noted between circulating TNF-alpha levels and the decrease in BI detected at the onset of the reactional episode. Evaluation of bacterial viability of M. leprae isolated from the reactional lesions showed no growth in the mouse footpads. Only 20% of the patients demonstrated specific immune response to M. leprae during ENL. Moreover, high levels of soluble IL-2R (interleukin-2 receptor) were present in 78% of the patients. Circulating anti-neural (anti-ceramide and anti-galactocerebroside antibodies) and anti-mycobacterial antibodies were detected in ENL patients' sera as well, which were not related to the clinical course of disease. Our data suggest that bacterial killing is enhanced during reactions. Emergence of specific immune response to M. leprae and the effective role of TNF-alpha in mediating fragmentation of bacteria still need to be clarified. Dados recentes sugerem que o curso clínico dos estados reacionais na lepra está estritamente relacionado à liberação local ou sistêmica de citocinas. Neste estudo, pacientes com ENL (erythema nodosum leprosum) foram grupados segundo a intensidade de seus sintomas clínicos. Os aspectos clínicos e imunológicos do ENL e os efeitos desses parâmetros na carga bacilar foram estabelecidos em conjunção com a resposta imune in vitro desses pacientes, a antígenos microbacterianos. Em 10 de 17 pacientes testados, o índice bacteriano (IB) foi reduzido cm pelo menos 1 log desde o diagnóstico da lepra até o aparecimento do primeiro episódio reacional, comparado a uma redução esperada de 0.3 log no grupo não reacional no mesmo período de MDT (multidrogaterapia). Entretanto, nenhuma diferença na taxa de redução do IB foi notada no final da MDT entre os pacientes ENL e os lepromatosos não reacionais. Assim também, embora os níveis de TNF-alfa (fator de necrose tumoral) estivessem aumentados no soro de 70,6% dos pacientes com ENL testados, nenhuma relação foi notada entre os níveis circulantes de TNF-alfa e a diminuição do IB detectada no aparecimento do primeiro episódio reacional. A avaliação da viabilidade bacteriana do M. leprae isolado de lesões reacionais não mostrou crescimento na pata de camundongo. Somente 20% dos pacientes demonstraram resposta imune específica ao M. leprae durante o ENL. Além disso altos níveis de IL-2R (receptor de interleucina 2) solúvel estiveram presentes em 78% dos pacientes. Anticorpos circulantes anti-nervo (anti-ceramídio e anti-galactocerebrosídio) e anti-micobacterianos foram também detectados no soro dos pacientes, e não estiveram relacionados ao curso clínico da doença. Nossos dados sugerem que a morte bacteriana está aumentada durante as reações. A emergência de resposta imune específica ao M. leprae e o papel efetivo do TNF-alfa na mediação de fragmentação bacteriana necessita ainda ser esclarecida

Objective: To compare the efficacy and the period of use of tocilizumab and infliximab during treatment of rheumatoid arthritis patients. Methods: The period of use of two biologics with different mechanisms of action were compared in treatment of rheumatoid arthritis patients. Results: Both medications showed efficacy, but the period of use with no loss of efficacy was longer in patients receiving tocilizumab when compared to infliximab. Conclusion: Tocilizumab maintains a period of use significantly longer as compared with infliximab in patients with rheumatoid arthritis treated at a single organization.

Patents for many key biological agents will soon expire. Third-party companies are, therefore, in the process of developing their own versions, termed biosimilar agents, of these innovator products. However, manufacture of biosimilar agents is complicated by the requirement for their production in biological systems, small variations in which can influence the structure, activity and metabolism of the biosimilar product. The development of biosimilar therapies for the treatment of patients with rheumatic diseases could potentially result in substantial cost savings for patients and health care providers, and consequently, increased availability of effective therapies. However, legislation that regulates the manufacture, registration and approval of biosimilar therapies varies considerably between different countries. In addition, major safety and efficacy concerns must be addressed before a rheumatologist can routinely substitute an innovator pharmaceutical with a biosimilar product.

Em 26 pacientes com diagnóstico definido de esclerose múltipla foram colhidas amostras de sangue e pesquisados os receptores solúveis de interleucina-2 (RsIL-2). Para tal os pacientes foram divididos em dois grupos: um constituído de 14 pacientes em surto da doença e o outro com 12 pacientes em remissão da moléstia. Além destes, procedeu-se a colheita de material para a mesma pesquisa em 8 pacientes com outras doenças neurológicas. Os resultados demonstraram aumento dos RsIL-2 em 50% dos casos do grupo de pacientes em surto da doença, fato não observado nos demais pacientes dos demais grupos. Estes resultados confirmam a hipótese da ativação de células Tem pacientes em surto de esclerose múltipla, corroborando a hipótese da existência de um desequilíbrio imunológico na doença.

The present study aimed at describing the implementation process of a national registry in a developing country (Brazil) and at reporting the main preliminary results of the BiobadaBrasil registry.Through a PANLAR agreement, the Biobadaser protocol was used as a model for implementing the new registry in our country. During the first two years of this effort, the original protocol was adapted, translated, and presented to all Brazilian rheumatologists. For ten months, data of 1,037 patients (750 subjects treated with biological drugs and 287 control subjects) from 15 centers were collected.Most patients had rheumatoid arthritis (RA) (n = 723). Infliximab was the most frequently used anti-TNF agent, and the total exposure to biologic drugs was 2,101 patient-years. The most common reason for interrupting drug use was lack or loss of efficacy (50%), while 30% withdrew from the treatment arm due to adverse events. Three cases of tuberculosis were observed in the biologic group, with an incidence higher than that of the general Brazilian population. Infections were observed in 23% of the biologic group, and the upper respiratory tract was the most commonly affected site. Only one case of tuberculoid leprosy was observed. No deaths or malignancies attributed to drug effects were observed as of February 2010.The implementation of the BiobadaBrasil registry was successful, and, although recent, the registry has provided important data.

Autoimmune hemolytic anemia (AIHA) is a disease where patients produce antibodies against erythrocytes directed towards membrane glycoproteins adsorbed onto the erythrocyte surface. Drugs and other associations have been implicated. It is described and discussed a case of livedo reticularis associated with AIHA treated with peripheral blood stem cell transplantation (PBSCT) that went into full remission for 10 years. After that period the patient relapsed and was treated with antibody anti-CD20, rituximab, and is now in full remission. The role of PBSCT and rituximab in the treatment of AIHA will be discussed.

Autologous stem cell transplant is one of the therapies employed in the treatment of primary amyloidosis or AL. The authors report on a 46-year-old patient with bilateral periorbital hematomas, macroglossia who presented, during the investigation, IgG-Kappa paraprotein in serum. The diagnosis of primary amyloidosis or AL was confirmed and the treatment proposed consisted of high-dose melphalan as conditioning regimen before autologous stem cell transplant, which determined complete remission of the disease, along with the disappearance of clinical signs and absence of the monoclonal component.

Recently, a number of biologic agents have been tested as therapies forautoimmune diseases, revealing new insights into the pathogenesisof immune-mediated diseases that revolutionized the management ofsuch patients. In the present article, we report on biological therapymodalities in autoimmune diseases. These patients have beensuccessfully treated by these agents, so that a better knowledge ontheir management and the risks of harm has become part of goodclinical practice.

A Somatostatin analogue (SMS201-995) was used to treat amyloidosis associated diarrhea. Considerable improvement was observed suggesting a beneficial effect of this drug on the diarrhea observed in some patients with amyloid associated neuropathy.

Patients with solid Neoplasms requiring therapy with inter feron had serial measurements of IL-1, TNF, and SAA Evalua ted before and after repeated injections. TNF elevations were observed in all patients while IL-1 and SAA showed no significant changes.

The fine structure and plasma membrane receptors of explant and monolayer cells of normal rabbit synovium were studied. In explants about 10% of the cells were round and formed rosettes with IgC and C3 markers, whereas the remaining cells were stellate, resembled young fibroblasts, and had no receptors for IgG and complement. Monolayer cells looked like fibroblasts, produced fine extracellular fibrils and hyaluronate, and formed no rosettes. Thus early cultures contain both macrophages and fibroblasts but only the latter persist in monolayer.

Serum amyloid protein A (SAA), the precursor of secondary amyloid protein, is elevated in chronic diseases which are associated with an increased incidence of amyloid. However, SAA is also elevated in acute bacterial and viral infections and somes forms of cancer. The murine model of casein-induced amyloidosis was studied to determine the relationship between SAA production and amyloid deposition. SAA levels measured by radioimmunoassay were found to be as high as 200 times the normal level in CBA/J mice receiving daily parenteral casein. After a single injection of casein the SAA level was elevated by 3h and peaked by 12-18 h. Similar levels were found in casein-treated A/J mice, a strain less susceptible to the induction of amyloid. Parenterally administered bovine serum albumin, which has low potential for amyloid induction, gave SAA levels in CBA/J and A/J mice comparable to casein treatment. These data show that, while SAA levels are elevated during chronic antigenic stimulation, there are other factors involved in amyloid formation. These factors may include alterations in the degradation of SAA by the reticuloendothelial system caused by substances such as casein. Nude (athymic) mice were shown to attain high levels of SAA after receiving casein parenterally. Therefore, thymus-derived lymphocytes are not necessary for the synthesis of SAA.

The presence of B, T, and monocyte markers were studied on the spleen and peripheral blood mononuclear cells from two patients with leukemic reticuloendotheliosis. A high proportion of cells from both patients bore a receptor for cytophilic antibody, both in suspension and frozen tissue section. Cells in suspension lacked surface immunoglobulins or a receptor for sheep red blood cells. These results favor the evidence that "hairy cells" are monocytic in origin.

NE OF THE MAJOR QUESTIONS in modern immunology is how thymusderived (T) cells and bone marrow-derived (B) cells interact to achieve mutual cooperation and negative feedback control. 1 It is becoming clear that disturbances in the intricate balance between T and B cells may result in a variety of clinical disorders, especially those considered to be autoimmune syndromes. 2 This development is largely due to the fact that in experimental animal models and in the clinical presentation of these disorders, several immunologic abnormalities leading to tissue injury have been well documented and shown to be a prerequisite for the manifestation of the disease state. This review will briefly summarize the abnormal interactions between T and B cells and the way in which their derangement may lead to autoimmunity. Special attention will be placed on the enumeration of peripheral blood lymphocytes by membrane-associated cell markers and the possible pathogenetic, diagnostic, and prognostic significance of these findings. DEFINITIONS AND NOMENCLATURE For the purpose of this review, T cells will be defined as thymus-derived lymphocytes capable of initiating delayed hypersensitivity and allograft reactions, elaborating lymphokines, and participating in the defense of the host against in

Evidence is presented that T cell impairment appears to be specifically related to the pathogenesis of experimental amyloidosis. This conclusion is based on the finding that thymosin administration improves T cell function as measured by mitogen stimulation of spleen cell suspension and at the same time reduces the incidence and severity of amyloid disease in casein-treated mice.

Eighteen volunteers in two study groups were inoculated with influenza A (H3N2) and their peripheral blood T, B and null cells enumerated at subsequent intervals. Infection with wild-type virus or with a live, attenuated virus vaccine markedly reduced the proportion and absolute number of T-cell rosettes 24 hours after inoculation. T-cell depression preceded the onset of clinical illness in symptomatic subjects, continued during illness, and returned to normal with recovery. T-cell lymphopenia was most pronounced in volunteers infected with wild-type virus and was accompanied by an increase in null cells. Lymphocytes from six wild-virus recipients with T-cell leukopenia were incubated in vitro with a calf-thymus extract (thymosin), significantly increasing the percentage of T rosettes in all six subjects (P< 0.01). These data indicate that influenza is accompanied by pronounced quantitative and functional changes in T cells. (N Engl J Med 294:1208–1211 1976)

Serum immunoglobulin abnromalities in nonfamilial and systemic primary amyloidosis are distinct from those seen in multiple myeloma and more closely resemble those seen in benign monoclonal gammopathy. Surface lymphocyte characteristics also differentiate amyloid patients with or without monoclonal immunoglobulins from those with malignant B-cell dyscrasias. In vitro lymphocyte transformation with phytohemagglutinin and pokeweed mitogen is normal in amyloidosis, but T-cell function is significantly depressed in both primary and secondary amyloid disease as measured by concanavalin A responses.

The absolute number and proportion of B and T lymphocytes in the peripheral blood was determined in 16 active and 11 inactive patients with systemic lupus erythematosus. The total number of B and T lymphocytes was significantly reduced when compared to normals. The population of thymus-derived cells seems to be the one predominately affected. These abnormalities improve, but are not completely reversed, when patients are in remission.

Phytohemagglutinin (PHA) induced cell cytotoxicity was studied in man using chromated chicken red blood cells (CRBC) as target cells. A phagocytic, adherent monocyte was found to be necessary for lysis of target cells. Results using E rosette depletion showed that this procedure markedly increased mitogen-induced cellular cytotoxicity (MICC). Carbonyl iron treatment of peripheral blood cell suspensions to remove phagocytic cells abolished MICC, as did removal of adherent cells by glass wool columns. Complement mediated lysis of B cells did not substantially reduce MICC. However, pretreatment of cells with silica or hydrocortisone did reduce MICC. The mechanism of mitogen-induced lysis appears to require direct cell contact between effector cells and target cells.

In order to characterize the T- and B-cell populations of inflammatory arthritides, synovial fluid and peripheral blood lymphocytes from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), and rheumatoid variant diseases (RV) were studied. Normal peripheral blood lymphocytes were examined as controls. T cells were identified by spontaneous sheep red blood cell (E) rosette formation. B cells were determined by complement receptor lymphocyte (EAC) rosette formation and by the presence of surface immunoglobulins (SIg) utilizing fluoresceinated polyvalent antiglobulin. Synovial fluids were analyzed in terms of duration, mucin quality, white cell count, and differential. Synovial fluid and peripheral blood lymphocytes from patients with RA and RV were distributed in T- and B-cell percentages similar to those found in normal peripheral blood. In contrast, significant T-cell depression was observed in the percentage of synovial fluid and peripheral blood lymphocytes of SLE and JRA patients. This depression was apparent in comparison with normal peripheral blood and with the synovial fluid and peripheral blood from RA patients. B-cell percentages were similar in all patient groups and in comparison to normal peripheral blood lymphocytes. No differences were noted in B-cell percentages when the EAC and SIg techniques of identification were compared. The percentage of cells bearing neither T- nor B-cell markers (null cells) was enumerated for each patient group and found to be significantly elevated in the synovial fluid and peripheral blood of SLE and JRA patients. Though the mean synovial fluid and peripheral blood null cell percentages in RA patients were similar to those in controls, a definite bimodal distribution was found in the synovial fluids. These data suggest that evaluation of T-, B-, and null-cell populations may be clinically useful in differentiating patients with SLE and JRA from those with rheumatoid arthritis and variant diseases.

We evaluated T-lymphocyte subsets in 18 patients with active untreated uveitis and in 20 controls by monoclonal OKT (Ortho-Kung-T cell) antibodies. Both OKT4- and OKT8-positive cells were detected in the aqueous humor of patients with uveitis. The percentage of OKT4-positive cells (21.1 +/- 7.4) was larger than that of OKT8-positive cells (15.2 +/- 5.3) and the OKT4-OKT8 ratio was 1.40 +/- 0.3. A comparison of aqueous humor and peripheral blood cells from patients with uveitis showed diminished frequencies of OKT4- and OKT8-positive cells. The OKT4-OKT8 ratios were not significantly different. A comparison of peripheral blood cells from patients with uveitis and from controls showed that patients with uveitis had lower OKT4-OKT8 ratios. Lower percentages of OKT4-positive cells were also observed in the peripheral blood cells of patients with uveitis.

Familial amyloid polyneuropathy (FAP) is an inherited disorder, characterized by the extracellular deposition of fibrillary amyloid protein in various organs.