Plasma postheparin lipolytic activity (PHLA) was measured on 50 patients with systemic lupus erythematosus (SLE). Plasma PHLA was significantly decreased in SLE patients. This decrease was most striking in the acute phase of the disease. There was a close relationship between decreased PHLA and immunologic factors indicative of the acute phase of SLE. These immunologic factors included shaggy antinuclear antibody pattern, low serum complement titer, high DNA antibody titer, mixed cryoglobulin and lumpy glomerular pattern by immunofluorescent staining.</p

Kawanishi, Koichi

Nagase, Masayuki

Ofuji, Tadashi

Ueda, Hidenori

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Decreased plasma postheparin lipolytic activity in systemic lupus erythematosus

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 31, Issue 5 1977 Article 4OCTOBER 1977Decreased plasma postheparin lipolyticactivity in systemic lupus erythematosusKoichi Kawanishi∗ Hidenori Ueda†Masayuki Nagase‡ Tadashi Ofuji∗∗∗Okayama University,†Okayama University,‡Okayama University,∗∗Okayama University,Copyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Decreased plasma postheparin lipolyticactivity in systemic lupus erythematosus∗Koichi Kawanishi, Hidenori Ueda, Masayuki Nagase, and Tadashi OfujiAbstractPlasma postheparin lipolytic activity (PHLA) was measured on 50 patients with systemiclupus erythematosus (SLE). Plasma PHLA was significantly decreased in SLE patients. Thisdecrease was most striking in the acute phase of the disease. There was a close relationshipbetween decreased PHLA and immunologic factors indicative of the acute phase of SLE. Theseimmunologic factors included shaggy antinuclear antibody pattern, low serum complement titer,high DNA antibody titer, mixed cryoglobulin and lumpy glomerular pattern by immunofluorescentstaining.∗PMID: 146403 [PubMed - indexed for MEDLINE] Copyright c©OKAYAMA UNIVERSITYMEDICAL SCHOOLActa Med. Okayama 31, 319-324 (1977\DECREASED PLASMA POSTHEPARIN LIPOLYTICACTIVITY IN SYSTEMIC LUPUSERYTHEMATOSUSKoichi KAWANISHI, Hidenori VEDA, Masayuki NAGASEand Tadashi OFUJIThird Department of Internal Medicine, Okayama University Medical School,Okayama 700, Japan (Director: Prof. T. Ofuji)Received July 25, 1977Abstract. Plasma postheparin lipolytic activity (PHLA) was mea-sured on 50 patients with systemic lupus erythematosus (SLE). PlasmaPHLA was significantly decreased in SLE patients. This decreasewas most striking in the acute phase of the disease. There was a closerelationship between decreased PHLA and immunologic factors indi-cative of the acute phase of SLE. These immunologic factors includedshaggy antinuclear antibody pattern, low serum complement titer,high DNA antibody titer, mixed cryoglobulin and lumpy glomerularpattern by immunofluorescent staining.Hyperlipoproteinemia may be present in various collagen diseases (1). Type1 and type 3 hyperlipoproteinemias combined with decreased postheparin lipoly-tic activity (PHLA) have been reported in a few cases of systemic lupus erythe-matosus (SLE) (2-4). In a previous study of 67 SLE patients, we found thatabout 40% of patients had type 2a hyperlipoproteinemia and 40% had type 4hyperlipoproteinemia (5). In the present study, plasma PHLA and some selectedimmunological measures were studied in a group of SLE patients.MATERIALS AND METHODSA total of 50 consecutive hospitalized SLE patients was examined (5 males,45 females; aged 12-51). The criteria of SLE diagnosis were according to Cohenet al, (6). A few patients were examined during both the acute and remissionperiods, as defined by Schur and Sandson (7). The diagnoses were made byone author (H.D.) independent of the PHLA values. All patients were beingtreated with steroids. Most patients in the acute phase were receiving a dailydose of 30mg of prednisolone, and most patients in remission were receivinga daily dose of lOmg of prednisolone. Other immunosuppressive agents usedtogether with prednisolone were: cyclophosphamide (lOOmg/day in acutephase and 5Omg/day in remission, 11 patients); azathioprin (lOOmg/day inacute phase and 50mg/day in remission, 7 patients); and 6-mercaptopurine(50mg/day in acute phase and 25mg/day in remission, 5 patients). Thirty, non-obese hospital staff members served as control subjects (15 males, 15 females;3191Kawanishi et al.: Decreased plasma postheparin lipolytic activity in systemicProduced by The Berkeley Electronic Press, 1977320 k. KAWANISHI, H. VEDA, M. NAGASE and T. OFUl!aged 20-40). None of the control subjects had plasma lipid abnormalities. InSLE patients, blood samples were obtained 10, 20 and 30min after an intra-venous injection of heparin sodium at O. I mg/kg of body weight. In normalcontrols, blood samples were obtained at the same time periods after the samedose of heparin injection as the patients.Plasma PHLA was determined by a slight modification of the technique ofFredrickson et al. (8). Glass-stoppered tubes containing a.5ml of 5% bovinealbumin (Fraction V), 5mg of coconut oil emulsion (Ediol), a.2ml of ammo-nium chloride and O.2ml of plasma in a total volume of l.Oml were incubatedat 37°C for 30min. Free fatty acid (FFA) concentrations in O.2ml of the sub-strate-plasma mixture were determined by the method of Itaya and Ui (9).PHLA was calculated from the difference in FFA concentration between theincubated tube and control tube. The values were expressed as pEqFFA/ml,min plasma.Results were obtained from most patients for each of the following: anti-nuclear antibodies (ANA) separated into shaggy, diffuse and speckled patterns(10, 11); serum complement titer (CH50) (12); DNA antibody titer (13); cryo-globulin of IgG and IgG-IgM mixed type (15); and immunofluorescent stainingof biopsied kidney differentiated into linear, mesangial, granular or lumpypatterns of glomeruli (16). In biopsied patients plasma PHLA values weredetermined no later than 2 weeks after biopsy. Histologic examinations wereconducted on biopsied specimens stained by hematoxylin-eosin.RESULTSMean plasma PHLA values (,.uEqFFA/mljmin) of normal subjects were0.249 at 10 min; 0.192 at 20 min; and 0.039 at 30 min. There were no differ-ences between the sexes in the result for the control plasma PHLA. SLE plasmaPHLA was significantly 10 ,er compared to normal subjects (Fig. 1). The SLEpatient response was prominent in the acute phase of the disease. The meanacute patient values v.ere 0.05'0 at lOmin; 0.0)7 at 20 min, and 0.019 at SO min.PHLA values in remission were 0.111 at 10 min; 0.070 at 20 min; and 0.040 at20 min, There were no differences between the sexes in the results for theplasma PHLA of SLE patients PHLA values were not related to the type ofimmunosuppressive agents used in treatment.Patients with the shaggy ANA pattern showed significantly lower plasmaPHLA compared with patients with diffuse or speckled patterns (Table 1). Apositive correlation was prfs~nt between PHLA and serum compl' ment titer(Fig. 2). The DNA antibody titer showed an inverse correlation with PHLA(Fig. 3). Patients with positive cryoglobulin showed lower plasma PHLA valuesthan patients with negative cryoglobulin; patients with IgG-IgM mixed cryo-globulin showed decreased plasma PHLA values compared with IgG type cryo-globulin (Table 1). Patients with lumpy immunofluorescent patterns showed a2Acta Medica Okayama, Vol. 31 [1977], Iss. 5, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol31/iss5/4Postheparin Lipoiytic Activity in SLE 321D NORMAL RANGE 1M ± sorO ··rO··r:......rDIJ: ... rI . :i: ··.. :r .. . I'3'j~ I ... ..... .. r;fj;... ...· ·:r· ...... .ACUTE PHASE I REMISSION ACUTE PHASE I REM 15SI0 N ACUTE PHASE I REMISSION10 min 20 min 30 min0.1000.200}JEqFFA/ml/min0.300Fig. 1. Plasma PHLA levels at three time periods after heparin administration(0.1 mg/kg) in the acute and remission periods of SLE patients. Plasma PHLA wassignificantly lower in SLE patients compared to the control values (P<.OOl at 10, 20and 30min). Plasma PHLA levels during the acute phase were depressed comparedto PHLA levels during remission (P<.Ol at 10, 20 and 30 min).pEqFFA/ml/min0.300 r= 0.485( p<O.OI)••0.200<[-.JI0..0.100•••••• •• •• •• • •••• •• • •••• • •••• •• • • •• • • • •• ••• • ••••10 20 30SERUM COMPLEMENT TITER40Fig. 2. Relationship between plasma PHLA 10 min after heparin administra-tion and serum complement titer in SLE patients. Plasma PHLA level correlatedpositively with serum complement titer (r=0.485).3Kawanishi et al.: Decreased plasma postheparin lipolytic activity in systemicProduced by The Berkeley Electronic Press, 1977322 K. KAWANiSHI, H. VEDA, M. NAGASE and T. OFU]I}'EqFFA/ml/min0.300r= -0.445(p<O.OI)•0.200•« •.-l •I • •0... e • •••0.100• ••• • • •••• •••• •• •• ••• •• • •• •• ••• ••10 20 30 40CNA t\.NTI80DY TITER50 (%)Fig. 3. Relationship between plasma PHLA 10 min after heparin administra-tion and DNA antibody titer in SLE patients. Plasma PHLA level correlated in-versely wi th DN A antibody titer Ir = -- 0.445).TABLE 1. RELATIONSHIPS BETWEEN IMMl'NOLOGIC MEASURES AND PLASMA PHLALEVELS l,uEQFF A/ML/MINI IN SLE PATIENTSAntinuclearantibodies(number ofpatients)PHLA (Mean ± SD)10 minafter heparininjectionCryoglobulin(number ofpatients)PHLA (Mean ± SD)10 minafter heparininjectionImmunofluorescentpatterns ofglomeruli(number ofpatients)PHLA (Mean10 minafter heparininjectionShaggy (23)0.058 ± 0.029*IgG-IgM (810.060 0.022 CLumpy (4)0.042 0.013""Diffuse (21)0.0~5 ::J= 0.044IgG (13)0.095 ± 0.037Granular (14)0.073 +: 0.029Speckled Ill)0.131 ± 0.066Negative (5)0.116 =!-: 0.033Mesangial andlinear (12)0.110 ± 0.035---------------------------* P < .05 with diffuse pattern; p .01 with speckled pattern+ P < .05 with IgG; P < .01 with negative cryoglobulinP < .01 with mesangial and with linear immunflouorescent patterns4Acta Medica Okayama, Vol. 31 [1977], Iss. 5, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol31/iss5/4/Postheparin Lipolytic Activity in SLE 323significant PHLA depression compared to patients with mesangial or linear im-munofluorescent patterns (Table I). Most patients with mesangial and linearpatterns showed normal or minimal histological changes in the glomeruli. Pa-tients with granular patterns showed focal or diffuse proliferative glomerulone-phritis and membranous glomerulonephritis. Most cases with lumpy patternsshowed membranous glomerulonephritis including wire-lOOp lesions.DISCUSSIONSeveral distinctive immunologic features have been reported in the acutephase of SLE. These include shaggy ANA pattern (11), low complement levels(7), high DNA antibody titers (14), the presence of mixC'J (IgG-IgM) cryoglo-bulin (15), an r1 a lumpy immunofluorescent pattern of biopsied glomeruli (16).In the present study, plasma PHLA was measured on 50 patients with SLE.Plasma PHLA was significantly decreased in SLE patients and most strikingly inthe acute phase of the disease. A close relationship was present between (e-creased PHLA and immunologic factors indicative of the acute phase of SLE.Glueck et at. (2,3) reported SLE accompanied by acquired type I hyperlipo-proteinemia, dysglobulinemia and heparin resistance in three patients. In thesecases a decrease was found in plasma PHLA, triglyceride lipase and monoglyce-ride hydrolase. These investigators demonstrated that the plasma PHLA de-pression was due to the association of the heparin-binding immunoglobulin withexogenous hyperlipoproteinemia. Beaumont and Lemort (17) also reported im-munoglobulins with antiheparin activity. Stern et al. (4) reported acquired type3 hyperlipoproteinemia in two patients with SLE. PHLA was decreased in bothpatients. In one of these patients after adrenocortical steroid treatment, thePHLA value returned to normal concomitantly with the disappearance of thetype 3 hyperlipoproteinemia. In a previous study in our laboratory (5), SLEpatients with decreased PHLA often showed elevated plasma triglyceride. Thepathophysiology of SLE is extremely complicated, and various factors are likelyto be involved in the SLE lipid metabolism. The decreased PHLA is probablyrelated not only to heparin binding with serum but to other factors of immuno-logic, metabolic and therapeutic consequence.REFERENCES1. Parra, C. A., Abaurre, R. and Rivero, 1.: Collagen diseases associated with type 4 hy-perlipoproteinemia. Arch. Dermatol. Forsch. 251, 123-127, 1974.2. Glueck, C.]., Levy, R.I., Glueck, H.I., Gralnick, H.R., Greten, H. and Fredrickson, D.S.: Acquired type 1 hyperlipoproteinemia with systemic lupus erythematosus, dysglo-bu1inemia and heparin resistance. Am.]. Med. 47, 318-324, 1969.3. Glueck, C. j., Kaplan, A. P., Levy, R. 1., Greten, H., Gralnick, H. and Fredrickson, D. S.:A new mechanism of exogenous hyperg1yceridemia. Ann. Intern. Med. 71, 1051-1062,1969.5Kawanishi et al.: Decreased plasma postheparin lipolytic activity in systemicProduced by The Berkeley Electronic Press, 1977324 K. KAWANISHI, H. VEDA, M. NAGASE and T. OFU]I4. Stern, M. P., Kolterman, O. G., McDevitt, H. and Reaven, G. M.: Acquired type 3 hy-perlipoproteinemia. Arch. Intern. Med. 130, 817-821, 1972.5. Nagase, M., Kawanishi, K., Ueda, H., Kurata, N. and Ofuji, T.: Serum lipids in SLEpatients. The Ryumachi 13, 497, 1973 (in Japanese).6. Cohen, A. S., Reynolds, W. E., Franklin, E. c., Kulka, J. P., Ropes, M. W., Schlman, L. E.and Wallase, S. L.: Preliminary criteria for the classification of systemic lupus erythe-matosus. Bull. Rheum. Dis. 21, 643-648, 1971.7. Schur, P. H. and Sandson, J. : Immunologic factors and clinical activity in systemic lupuserythematosus. N. Eng!. j. Med. 278, 533-538, 1968.8. Fredrickson, D.S., Ono, K. and Davis, L.L.: Lipolytic activity of postheparin plasmain hyperglyceridemia. j. Lipid Res. 4, 24-33, 1963.9. Itaya, K. and Ui, M.: Calorimetric determination of free fatty acids in biological fluids.J. Lipid Res. 6, 16-20, 1965.10. Beck, J. S.: Variations in the morphological patterns" autoimmune" nuclear fluores-cence. Lancet 1, 1203-1205, 1961.II. Casals, S. P., Friou, G. J. and Teague, P. 0.: Specific nuclear reaction of antibody toDNA in lupus erythematosus sera. j. Lab. Clin. Med. 62, 625-631, 1963.12. Mayer, M. M.: Procedure for titration of complement. In Experimental Immunochemiytry,ed. E. A. Kabat and M. M. Mayer, C. C. Thomas, Springfield, Illinois, pp. 149-153, 1961.13. Carr, R. I., Koffler, D., Agnello, V. and Kunkel, H. G.: Studies on DNA antibodiesusing DNA labelled with actinomycin D(3H) or dimethyl (3H) sulphate. Clin. Exp. Im-munol.4, 527-536, 1969.14. Casals, S. P., Friou, G. J. and Myers, L. L.: Significance of antibody to DNA in systemiclupus erythematosus. Arthritis Rheum. 7, 376-390, 1964.15. Barnett, E. V., Bluestone, R. and Cracchiola, A. III.: Cryoglobulinemia and disease. Ann.Intern. Med. 73, 95-107, 1970.16. Koffler, D., Agnello, V., Carr, R. I. and Kunkel, H. D.: Variable patterns of immuno-globulin and complement deposition in the kidneys of patients with systemic lupus ery-thematosus. Am. j. Patho!. 56, 305-316, 1969.17. Beaumont, J. L. and Lemort, N.: Une immunoglobuline anti-heparine dans un serumhyperlipidemique. (Une nouvelle variete d'hyperlipidemie par auto-anticorps). C. R.Acad. Sr. Paris, 271, 2452-2454, 1970.6Acta Medica Okayama, Vol. 31 [1977], Iss. 5, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol31/iss5/4

Decreased plasma postheparin lipolytic activity in systemic lupus erythematosus

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