RABC

Browse

Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes

PMID	Title	PublicationDate	abstract
1757934	Early undifferentiated connective tissue disease. I. Early clinical manifestation in a lar	1991 Sep	We identified a cohort of 410 patients with connective tissue disorders (CTD) of less than or equal to 1 year duration among the participating clinics of the Cooperative Systematic Studies of the Rheumatic Diseases Program. Fifty-seven had rheumatic arthritis (RA), 57 systemic lupus erythematosus, 37 poly/dermatomyositis, 46 scleroderma, and 213 early undifferentiated CTD, including patients with Raynaud's phenomenon, unexplained polyarthritis or at least 3 CTD manifestations such as rashes, myalgias, etc. Baseline clinical data are now being reported. The followup of these patients may prove to be valuable in understanding these diseases. To our knowledge no similar cohort of patients is available for further investigation.
2786697	IL-6 is the principal factor produced by synovia of patients with rheumatoid arthritis tha	1989	First, IL-6 is produced by synovial tissue of patients with rheumatoid arthritis (RA) and is the principal mediator produced by that tissue inducing differentiation of B-lymphocytes into antibody-forming cells. The Leu-1+ subset of B-lymphocytes is induced by IL-6 to secrete rheumatoid factor (IgM with anti-Fc gamma specificity). Second, the main cell types producing IL-6 in cells dissociated from RA synovial tissue are mononuclear leukocytes. Connective tissue type cells (synoviocytes) cultured from RA synovial tissue produce IL-6 in response to IL-1 beta, and IL-6 formation is increased by TGF-beta. Glucocorticoids strongly inhibit and PGE2 slightly inhibits IL-1-induced IL-6 mRNA expression in synoviocytes. Production of IL-6 increases when undissociated RA synovial tissue is maintained in culture, thus suggesting release from inhibition by a factor or factors not yet identified. Third, the major known local effect of IL-6 in RA synovial tissue is the augmentation of antibody formation and the major known systemic effect is the induction of the synthesis by the liver of acute-phase proteins, especially C-reactive protein. Levels of circulating C-reactive protein are reported to decrease in RA patients receiving long-acting antirheumatic drugs, which would be consistent with the interpretation that immature monocyte-derived macrophages are major producers of IL-6 in these patients.
2947307	The role of Ia positive T cells in patients with rheumatoid arthritis.	1986	In peripheral blood and synovial fluid of patients with rheumatoid arthritis (RA), increased levels of Ia antigen-positive (Ia+) T cells have been demonstrated. Therefore, we examined these Ia+ T cells in vitro to identify their role in the production of rheumatoid factor (RF) and to study the immunologic abnormalities of RA. When Ia+ T cells from peripheral blood of RA patients were added to pokeweed mitogen (PWM)-non-stimulated autologous B cells, the amount of IgM-RF production was 25.8 +/- 6.4 (mean +/- SE) (p less than 0.001) as compared to 16.0 +/- 4.6 ng/ml (mean +/- SE) in the presence of Ia-T cells. When Ia-OKT4+ cell fractions, obtained by excluding Ia+ T cells from OKT4+ cells, were added to B cells, the increase in IgM-RF production was markedly lower than that obtained with the OKT4+ cell fraction. These results indicate that the helper T cells which induce the production of IgM-RF may derive from the Ia+ OKT4+ cell fraction. B cells from rheumatoid synovial fluid produced IgM-RF levels as high as 102.7 +/- 19.2 ng/ml (mean +/- SE) even without stimulation. When T cells from autologous synovial fluid were added, IgM-RF production was not increased. These data suggest that B cells from RA synovial fluid had already been activated. When synovial fluid T cells were added to B cells from autologous peripheral blood, larger amounts of IgM-RF were produced as compared to experiments in which T cells from peripheral blood were added, suggesting that T cells from synovial fluid induced an enhanced IgM-RF production by B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
2752614	Endosteal bone loss after total hip arthroplasty.	1989 Aug	Femoral endosteal bone loss has been shown to be part of the natural aging process and may be a factor in femoral component loosening following total hip arthroplasty (THA). In this study, changes in the femoral medullary canal width in 30 patients with aseptic femoral loosening following primary THA were compared with 30 matched control patients. The rate of canal expansion on the operated side was twice that of the nonoperated side and four times that of the control. After the onset of symptoms in the failure group, the rate of femoral expansion of the operated side doubled. Iliac crest biopsies showed a decrease in male patients for osteoid surface and appositional and bone formation rates when compared with literature controls. These results suggest that femoral medullary canal expansion may be a factor in femoral component loosening following THA. The increased rate of canal expansion after the onset of symptoms demonstrates the need for early surgical intervention to avoid excessive bone loss.
2742403	What proteins are present in polyethylene glycol precipitates from rheumatic sera?	1989 Jun	The proteins present in 4% polyethylene glycol (PEG) precipitates of 10 normal sera and 60 samples from patients with rheumatic diseases were studied. A variety of immunochemical methods were used, including estimation of the percentages of total serum proteins precipitated by PEG, gel filtration analyses of the precipitates, and affinity chromatography with protein A and anti-immunoglobulin columns. Substantial amounts of protein were precipitated from normal sera. Many non-immunoglobulin proteins were precipitated from patients' sera, including fibronectin, haptoglobin, albumin, transferrin, and alpha 1-antitrypsin. Affinity chromatography with anti-immunoglobulin columns bound non-immunoglobulin proteins from PEG precipitates, but the protein A affinity column did not do so. The view that circulating antibody-antigen complexes alone are precipitated by 4% PEG is too simplistic; many non-immunoglobulin proteins are involved. They may either bind to immune complexes or be coprecipitated owing to non-specific protein aggregation.
1947669	Interleukin-6 localisation in the synovial membrane in rheumatoid arthritis.	1991	Polyclonal antibodies were raised in rabbits against Interleukin-6 (IL-6) by immunisation with a synthetic peptide of identical sequence to the amino terminal 12 amino acids of human IL-6. These antibodies reacted with recombinant IL-6 by ELISA and stained the cytoplasm of the IL-6 secreting bladder tumour cell line T24. Staining was abolished by prior incubation of the antibody with the IL-6 peptide. F(ab')2 fragments made by pepsin digestion of the IgG were immunopurified, labelled with biotin and retained activity in the biochemical and histological assays. Sections of synovial membrane from patients with rheumatoid arthritis (RA) were stained with these antibodies, using an immunoperoxidase technique, and cells containing IL-6 were domonstrated in the thickened synovial lining layer and also in a perivascular distribution in the deeper synovium. In osteoarthritis there were fewer cells in the lining layer and hence localisation appeared similar in both the interstitial area and lining layer. Double-staining techniques with mouse monoclonal antibodies against cell subset markers in five RA synovial membranes showed that up to 13% of T-cells and 19% of antibody-producing cells stained for IL-6. However, up to 70% of the macrophages contained IL-6 and these were found in close proximity to Ig-producing plasma cells. This study showed that macrophages were the major cells of the immune system in which IL-6 could be localised in RA, and suggests a role for locally produced IL-6 in the stimulation of rheumatoid factor production.
3124262	Impaired mitogen-induced interferon-gamma production in rheumatoid arthritis and related d	1988 Jan	Peripheral blood lymphocytes from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), Reiter's disease, osteoarthritis, and from healthy volunteers were investigated for interferon-gamma (IFN-gamma) production after mitogen activation. Phytohaemagglutinin stimulation revealed an impaired IFN-gamma production in RA, SLE, and PSS but normal levels in Reiter's disease and osteoarthritis. In RA this deficiency was also seen after pokeweed mitogen, OKT3, and concanavalin A activation. No major differences were found in interleukin 2 (IL-2) production and cell proliferation. The IL-2 receptor expression was reduced on stimulated RA lymphocytes. The deficient IFN-gamma production was compensated in RA by co-stimulation of PHA or OKT3 with phorbol myristic acetate (PMA). In addition, the combination of the calcium ionophore A 23187 and PMA induced a strong IFN-gamma secretion in all patient groups and in the controls.
2842416	Proinflammatory lipoxygenase products from peripheral mononuclear cells in patients with r	1988 Sep	The formation of 5-lipoxygenase products (5-hydroxyeicosatetraenoic acid [5-HETE], leukotriene B4 [LTB4], and leukotriene C4 [LTC4]) by polymorphonuclear and mononuclear leukocytes isolated from peripheral blood of patients with rheumatoid arthritis was evaluated and compared with the data obtained from a group of control subjects. Although the levels of arachidonic acid metabolites via 5-lipoxygenase pathway by stimulated polymorphonuclear cells were comparable between patients and controls, mononuclear leukocytes from patients synthesized, when stimulated, significantly greater amounts of 5-HETE, LTB4, and LTC4 than did cells isolated from normal subjects. In addition, the release of superoxide anion, stimulated by either a particulate or a soluble stimulus, was increased in mononuclear cells from patients. The enhanced capacity of peripheral mononuclear leukocytes isolated from patients with rheumatoid arthritis to generate proinflammatory metabolites of arachidonic acid and oxygenated species with bactericidal and tissue-damaging properties may contribute to the pathogenesis of this complex disease.
2948275	Immunoregulatory function of T8 and T4 cells from synovial fluid and blood of patients wit	1986 Dec	The suppressor effect of synovial fluid (SF) T8 cells and blood T8 cells on the pokeweed mitogen (PWM)-induced T4 cell-dependent immunoglobulin production of autologous blood B cells was studied in nine patients with chronic rheumatic diseases (six patients with rheumatoid arthritis (RA), one patient with juvenile RA, and two patients with other forms of chronic arthritis). The suppressor effect of SF T8 cells was of the same magnitude as that of equal numbers of blood T8 cells from patients and healthy controls. However, the relative number of T8 cells was higher among SF T cells than among blood T cells in several cases. Good synovial T8 cell suppression was also demonstrated in coculture experiments where SF T4 cells and B cells were used. In PPD (purified protein derivative of tuberculin)-stimulated cultures the suppressor effect of SF T8 cells as well as of blood T8 cells from patients and controls was lower than it was in PWM-stimulated cultures. In most patients SF T4 cells showed a much better PWM-induced helper function than did non-fractionated SF T cells. Thus the poor PWM induced helper effect of non fractionated synovial T cells was in some cases mainly due to the suppressor effect of T8 cells, whereas in some cases there was also a deficient helper function of synovial T4 cells.
1958086	Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthri	1991 Oct	As nucleotide catabolism increases during tissue injury the appearance of purine metabolites in inflamed synovial fluid might be of value in understanding the joint damage in inflammatory arthritides. In this study, therefore, synovial and plasma concentrations of hypoxanthine, xanthine, and urate in 16 patients with rheumatoid arthritis (three with psoriatic arthropathy) were analysed. It was found that their plasma concentrations of hypoxanthine were greater than those of a reference group of healthy subjects. The synovial fluid concentrations of hypoxanthine, xanthine, and urate were higher than corresponding concentrations in plasma. Positive correlations were found between the respective plasma and synovial fluid values of xanthine and urate. These findings indicate a local enhanced purine metabolism in inflamed joint tissue and diffusion of oxypurines from joint cavity to plasma. No relation was found between measured metabolites and disease duration, radiological joint findings, or synovial fluid cells. Except for a weak correlation between plasma urate and serum haptoglobin, measured purine metabolites were not related to laboratory measures of systemic inflammation.
3106416	Inhibition of human endothelial cell proliferation by gold compounds.	1987 May	Neovascularization has a role in the propagation of rheumatoid synovitis because the spread of mononuclear cell infiltration and the growth of pannus are dependent on the growth of new blood vessels. Growth of such vessels requires local endothelial cell (EC) proliferation. Inhibition of synovial EC proliferation, therefore, would have the potential to diminish rheumatoid inflammation. We have, therefore, studied the effects of gold sodium thiomalate (GST), auranofin, and gold chloride on the proliferation of human umbilical vein EC. GST suppressed both basal and EC growth factor-induced tritiated thymidine incorporation into EC in a dose-dependent fashion. Inhibition was observed with concentrations as low as 1 microgram/ml GST, 5 micrograms/ml gold chloride, and 0.1 microgram/ml auranofin, levels attainable in blood and synovium of patients. These results suggest that gold compounds have an antiangiogenic effect. The low concentrations inhibiting EC proliferation suggest that gold compounds may suppress rheumatoid synovitis by reducing the number of small blood vessels available for mononuclear cell infiltration and synovial tissue proliferation.
3764306	Fibronectin in polyethylene glycol precipitates: evidence for a role in immune complexes.	1986	Fibronectin is involved in the opsonic clearance of particulate material. It is present in plasma and synovial fluid and thus might be expected to have a role in the clearance of immune complexes. We have investigated this in a study of polyethylene glycol (PEG) precipitable material from the serum of patients with rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Fibronectin is a significant component of PEG precipitates but the amount present is influenced by the method of preparation: more precipitates at 4 degrees C than at 20 degrees C. Fibronectin precipitation by PEG was considered to be related to immune complexes because: there was no direct relationship between serum fibronectin levels and the amount present in PEG precipitates; radiolabelled purified isolated fibronectin did not precipitate in 4% PEG; there was a direct relationship between the amount of fibronectin in PEG precipitates and the amounts of immunoglobulin G, A, and M. These results indicate that fibronectin is involved in immune complexes in rheumatic diseases, though they do not show it has an important biological role in these circumstances.
3121256	Immunogenetics of collagen-induced arthritis.	1987	CIA is a unique experimental model of disease, which may be particularly relevant to the study of RA, since it represents a true autoimmune reaction against a major joint component. Since it represents a model of the association of MHC genes and disease, it has a broad relevance to the study of disease, particularly the contribution of class II MHC genes to autoimmunity. This disease model has been demonstrated in three species, and a marked influence of immunogenetic control is apparent. Native type II collagen is a large protein with a genetically conserved structure, giving rise to a number of cross-reactive antigen epitopes between species. Susceptibility to CIA correlates with an Ir directed against certain epitopes, and this autoimmune response appears to be controlled by MHC-linked genes. In the mouse, susceptibility has been specifically associated with variations in the I-A beta chain. The immunogenetic control may be effected through the T-cell recognition of the collagen molecule, resulting in antibodies and reactive cells with a specificity for native autologous type II collagen. Although the specificity of the anti-type II collagen response is the critical element in the generation of the autoimmune reaction, production of a high level of antibody is important, as well as a complement-fixing isotype. Cell-mediated immunity to type II collagen contributes to the disease chronicity, either through the generation of inappropriate T help, or a suppressor defect, and the production of factors. However, the precise sequence of events, from antigen recognition to joint damage, has yet to be elucidated fully. Some aspects of this experimental model bear a striking resemblence to RA. Hopefully, this experimental model will provide valuable insights into the significance of collagen autoimmunity and the contribution of class II genes to the pathology of arthritic disease.
3307471	Pleural fluid pH: diagnostic, therapeutic, and prognostic value.	1987 Sep	Measurement of pleural fluid pH has diagnostic, therapeutic, and prognostic implications in exudative pleural effusions (Table II). A parapneumonic effusion with a pleural fluid pH below 7.2 indicates an empyema is forming which necessitates chest tube drainage in all patients, whereas a pleural fluid pH over 7.3 does not require drainage. If the pH of a parapneumonic effusion is 7.2 to 7.3, serial pleural fluid pH measurements with clinical observation will help to determine the need for chest tube drainage. A pleural fluid glucose level of below 60 mg/dl and a lactic dehydrogenase level over 1,000 IU/dl in conjunction with a pleural fluid pH of 7.2 to 7.3 indicate an impending empyema. These findings are consistent with our clinical experience in patients with parapneumonic effusion. Tuberculous pleural effusions had a pleural fluid pH below 7.4 in all reported patients. This pH may be of value in distinguishing tuberculous pleural effusions from recent malignant effusions, which tend to have a higher pleural fluid pH, particularly if used in conjunction with other pleural fluid values, cell counts, and other clinical parameters. In patients with malignant pleural effusions, a pH of less than 7.3 is usually seen in those effusions present for several months and is associated with a lower glucose level and a higher white cell count and lactic dehydrogenase level. Results of cytologic study of the pleural fluid and pleural biopsy are often positive, there is poor response to sclerosing agents, and the prognosis is poor. A rheumatoid pleural effusion most often has a pleural fluid pH below 7.3. A pleural fluid pH below 6 is seen almost exclusively in esophageal rupture but rarely with empyemas, whereas a pleural fluid pH below 7 occurs in esophageal rupture, empyema, and rheumatoid pleural effusions. In pleural effusions secondary to congestive heart failure, the pH is almost always greater than 7.4 unless systemic acidemia coexists, in which case the pleural fluid pH is within 0.04 units of the simultaneous arterial pH. The major value of pleural fluid pH is to determine the need for chest tube drainage in parapneumonic effusions and to determine the response to sclerosing agents in patients with malignant pleural effusions. As with all diagnostic tests, the results should be interpreted in the context of other diagnostic tests of the pleural fluid and clinical aspects before diagnostic or therapeutic decisions are made.
1908361	Light chain ratios of serum immunoglobulins in disease.	1991 Jun	We have determined the individual kappa (kappa)/lambda (lambda) ratios of serum IgG, IgA, and IgM in normal subjects and patients with rheumatoid arthritis, systemic lupus erythematosus, hepatic cirrhosis and IgA nephropathy--40 in each group. Serum samples were first screened by agarose electrophoresis to exclude paraproteinaemia. Concentrations of IgG, IgA, and IgM were determined by enzyme-linked immunosorbent assay (ELISA). The kappa and lambda chain concentrations of each immunoglobulin class were assayed by an ELISA method first developed by us for the determination of kappa/lambda ratios. Our results showed that kappa/lambda ratios of serum IgA and IgM were significantly different from that of IgG in normal subjects and the 4 groups of patients studied (p less than 0.01). The kappa/lambda ratios of individual immunoglobulins in patients with rheumatoid arthritis, systemic lupus erythematosus and liver cirrhosis were similar to those of normal subjects. However, patients with IgA nephropathy displayed a distinctly lower IgA kappa/lambda ratio, suggesting a unique antibody response in the immunopathogenesis of this disease.
2481309	HLA-DR4 subtype frequencies in rheumatoid arthritis indicate that DRB1 is the major suscep	1989 Dec	Susceptibility to rheumatoid arthritis (RA) may be due to the presence of shared functional epitopes common to the HLA-DR beta chains of several RA-associated haplotypes. We have obtained direct evidence for this hypothesis by using the polymerase chain reaction and sequencing the DRB1 and DQB1 genes from RA patients. A highly conserved epitope present on DR beta chains of DR4 and DR1 haplotypes was found in 83% of 149 patients with classical or definite RA but was found in only 46% of 100 control individuals (P less than 0.0001). Two Dw subtypes of DR4 (Dw4 and Dw14) were associated with disease susceptibility but two other subtypes (Dw10 and Dw13) were not. Sequence differences between these subtypes implicate those residues around the putative antigen binding site of the DR beta molecule in the pathogenesis of RA. These data provide a basis for understanding host susceptibility to RA at a molecular level.
1658048	Constitutive expression of a 92-kD gelatinase (type V collagenase) by rheumatoid synovial	1991 Nov	Synovial fibroblasts freshly isolated from the rheumatoid joint are characterized by their marked connective tissue degradative ability. This phenotype includes the ability to secrete large amounts of the matrix-degrading metalloproteinases, collagenase, and stromelysin. We have found that another aspect of this phenotype is the constitutive expression at both protein and mRNA levels of a 92-kD gelatinolytic metalloproteinase, which is not secreted by normal dermal or lung fibroblasts and is immunologically cross-reactive with a type V collagenase expressed by activated macrophages and neutrophils. Expression of this 92-kD metalloproteinase confers upon the fibroblasts the capacity to degrade collagenase- and stromelysin-resistant interstitial elements, such as collagen types IV, V and XI. In contrast to the 92-kD metalloproteinase, a 68-kD gelatinase (type IV collagenase) was expressed by all fibroblast types studied, indicating that its regulation is distinct from that of the 92-kD gelatinase. To identify what cytokines may be important in the induction of the rheumatoid synovial phenotype, including expression of the 92-kD gelatinase, we exposed normal dermal fibroblasts to a number of cytokines including many known or considered likely to be present in rheumatoid synovial fluid and tissue. Although IL-1 beta, tumor necrosis factor-alpha, lymphotoxin, platelet-derived growth factor, and basic fibroblast growth factor were capable of stimulating fibroblasts to secrete collagenase, only tumor necrosis factor-alpha, lymphotoxin, and IL-1 beta were able to induce expression of the 92-kD gelatinase, demonstrating discordant regulation of the two metalloproteinases. Expression of the 68-kD gelatinase was independent of that of the 92-kD gelatinase, as demonstrated at the protein and mRNA levels. Late passage rheumatoid synovial fibroblasts, which no longer constitutively expressed the 92-kD gelatinase, displayed an accentuated response to IL-1 beta when compared to normal dermal fibroblasts. Thus, in addition to IL-1 beta, tumor necrosis factor-alpha or lymphotoxin may contribute to the expression of a specific rheumatoid synovial phenotype in vivo that is associated with progressive matrix destruction.
2783591	Immunohistochemical detection and immunochemical analysis of type II collagen degradation	1989 Feb	Articular cartilage destruction and loss of function in arthritic diseases involves proteolytic degradation of the connective tissue matrix. We have investigated the degradation of cartilage collagen by developing immunochemical methods that permit the identification and analysis of type II collagen degradation in situ. Previously, a technique to specifically identify type II collagen degradation in situ in articular cartilage did not exist. These methods utilize a polyclonal antiserum (R181) that specifically reacts with unwound alpha-chains and CNBr-derived peptides, alpha 1(II)CB11 and alpha 1(II)CB8, of human and bovine type II collagens. The experimental approach is based on the fact that when fibrillar collagens are cleaved the helical collagen molecule unwinds, exposing hidden epitopes. Here we demonstrate the use of R181 in studying type II collagen degradation in bovine articular cartilage that has been cultured with or without IL-1 and in human normal, rheumatoid, and osteoarthritic articular cartilages. Compared to cartilages either freshly isolated or cultured without IL-1, bovine cartilage cultured with IL-1 for 3-5 d showed an increase in both pericellular and intercellular immunohistochemical staining. Extracts of these cartilages contained type II collagen alpha chains that were increased in amount after culture with IL-1 for 11 d. In addition, culture with IL-1 resulted in the appearance of alpha chain fragments of lower molecular weight. All human arthritic tissues examined showed areas of pronounced pericellular and territorial staining for collagen degradation as compared with non-diseased tissues, indicating that chondrocytes are responsible in part for this degradation as compared with non-diseased tissues. In most cases rheumatoid cartilage was stained most intensely at the articular surface and in the deep and mid-zones, whereas osteoarthritic cartilage usually stained more in the superficial and mid-zones, but less intensely. Distinct patterns of sites of collagen degradation reflect differences in collagen destruction in these diseases, suggesting possible different sources of chondrocyte activation. These experiments demonstrate the application of immunological methods to detect collagen degradation and demonstrate an increase of collagen degradation in human arthritides and in IL-1-treated viable bovine cartilage.
3665203	Do viruses play an etiologic role in ankylosing spondylitis or psoriatic arthritis?	1987 Nov	High venous blood levels of 2-5A, an adenylic acid polymer synthesized in the presence of double-stranded RNA and considered as a viral replication indicator, have been found in blood samples from ankylosing spondylitis and psoriatic arthritis patients, but not from patients with seropositive rheumatoid arthritis or acute chondrocalcinosis. These findings suggest the possibility that ankylosing spondylitis and psoriatic arthritis might be virus-induced diseases.
3240982	Amino acid composition and NH2-terminal amino acid sequence of human phospholipase A2 puri	1988 Sep	The amino acid composition and partial NH2-terminal amino acid sequence of an extracellular phospholipase A2 in human rheumatoid synovial fluid were determined. The predominant amino acids in the phospholipase A2 were cysteine, glycine, arginine, and lysine, suggesting that it is a basic one. The NH2-terminal 34 amino acids were found to be as follows: Asn-Leu-Val-Asn-Phe-His-Arg-Met-Ile-Lys-Leu-Thr-Thr-Gly-Lys-Glu-Ala-Ala-Leu- Ser-Tyr-Gly-Phe-Tyr-Gly-Cys-X-Cys-Gly-Val-Gly-Gly-Arg-Gly The enzyme contains Phe-5, Met-8, Ile-9, Tyr-24, Gly-25, Cys-26, Cys-28, Gly-29, Gly-31, Gly-32, and Gly-34 residues, all of which are conserved in most of the sequenced phospholipase A2. The remarkable feature of this enzyme was the absence of Cys-11, which is conserved in the "Group I" enzyme family. This is the first report concerning partial amino acid sequences of human non-pancreatic phospholipase A2.