Anticomplementary Effect Research Articles

Immunosupressive activity of opportunist pathogens of the infectious-inflammatory process in the urinary tract of men with calculous pyelonephritis

Objective - identification of pathogens of the infectious-inflammatory process of the urinary tract in men with calculous pyelonephritis, antilysozyme, anticomplementary, anti-immunoglobulin activity and inhibitory effect on the phagocytic activity of peripheral blood neutrophils.Material and methods. 34 strains of opportunistic taxa were isolated and identified by bacteriological method from 30 sick men aged 31 to 65 years (mean age 48.8 ± 4.27 years). These bacteria have antilysozyme, anti-complementary and anti-immunoglobulin activity, as well as the suppressive effect of supernatants of cultures of calculous pyelonephritis pathogens on the phagocytic activity of neutrophils in the peripheral blood of patients. The determination of the anti-complementary activity of bacteria was carried out using the principle, which includes testing the protective action of bacteria and their metabolic products against the growth of an indicator strain in the presence of a bactericidal substance (complement of blood serum). The antilysozyme activity of pathogens was investigated by a photometric method. Anti-immunoglobulin activity was studied by the method described in the work of I.S. Gaidash et al. Results. The majority of 27 (79.41%) isolated strains of Enterobacteriaceae (84%) and facultative anaerobic and aerobic gram-positive cocci (E. faecalis, S.saprophyticus) (66.67%) exhibit antilysozyme activity of varying degrees. The highest antilysozyme activity was found in the isolated strains of K. pneumoniae, 8.14% lower – in E. coli. Most (64.71%) of isolated strains of Enterobacteriaceae (68%) and gram-positive cocci (55.56%) from the urinary tract of men with calculous pyelonephritis exhibit anti-complementary activity. All isolated and identified taxa exhibit inhibitory activity against immunoglobulins of the main classes: Ig M, Ig G, and Ig A. K.pneumoniae inhibits immunoglobulins of all major classes, the concentration of Ig M decreases under the influence of this taxon by 22.36%, Ig G - by 26.88% and Ig A - by 19.61%.Conclusions. Opportunistic pathogens (E. coli, K. pneumoniae, P. mirabilis, E. cloaceae, S. marcescens, E. faecalis, S. saprophyticus) of the infectious-inflammatory process of the urinary tract in men with calculous pyelonephritis exhibit different levels of antilysozyme, anti-complementary activity; reduce the function of immunoglobulins Ig G (by 21.60%), Ig A (by 21.49%) and Ig M (by 14.30%), inhibit the phagocytic activity of neutrophilsby 15.74%, their capturing ability- by 22.59%.

Dendritic Polyglycerol Sulfate for Therapy and Diagnostics.

Dendritic polyglycerol sulfate (dPGS) has originally been investigated as an anticoagulant to potentially substitute for the natural glycosaminoglycan heparin. Compared to unfractionated heparin, dPGS possesses lower anticoagulant activity but a much higher anticomplementary effect. Since coagulation, complement activation, and inflammation are often present in the pathophysiology of numerous diseases, dPGS polymers with both anticoagulant and anticomplementary activities represent promising candidates for the development of polymeric drugs of nanosized architecture. In this review, we describe the nanomedical applications of dPGS based on its anti-inflammatory activity. Furthermore, the application of dPGS as a carrier molecule for diagnostic molecules and therapeutic drugs is reviewed, based on the ability to target tumors and localize in tumor cells. Finally, the application of dPGS for inhibition of virus infections is described.

Structural Features and Anti-Complement Activity of an Acidic Polysaccharide from Forsythia suspensa

Background: The complement system is an important host defence mechanism against the invasion of foreign materials. However, excessive or uncontrolled activation of the complement system might lead to severe complement-mediated disorders which are harmful to human bodies. There are still no desirable therapeutic compounds available on the market for complement inhibition. In recent years, researches have been focused on natural polysaccharides to modulate of the immune system because of their immunomodulatory activities and safety. In this study, Fs-8-ba2, a homogeneous acidic polysaccharide (MW ca. 7.2 kDa) was isolated from Forsythia suspensa and its anti-complementary effect was investigated. Method: The major primary structural features of Fs-8-ba2 were elucidated using HPGPC, IR, absolute configuration, component analysis and methylation analysis, periodate oxidation, carboxyl reduction partial acid hydrolysis, and NMR spectroscopy, etc. To identify the anti-complementary activity of Fs-8-ba2, the hemolytic assays through the classical pathway (CP) and the alternative pathway (AP) of complement system in vitro were taken. Results: The backbone of Fs-8-ba2 was composed of 7 homogalacturonan (HG) and 2 rhamnogalacturonan (RG-I) moieties with the side chains attached at O-4 of 1,2,4-linked α-L-Rha in the RG-I moieties. The anti-complement assay showed that the native acidic polysaccharide (Fs-8-ba2) possessed stronger inhibitory effect on the complement activation than the carboxyl-reduced polysaccharide (Fs-8-ba2re) through the classical (IC50: 0.311 ± 0.020 mg/mL vs. 3.292 ± 0.032 mg/mL) and alternative pathways (IC50: 0.218 ± 0.015 mg/mL vs. no activity). It indicated that the anti-complement effect of pectic polysaccharide was related to GalA content (carboxyl group). Preliminary mechanism studies by using complement-depleted sera indicated that Fs-8-ba2 selectively interacted with C1q, C1r, C1s, C2, C3 and C9, but not C4 and C5. Conclusion: These results suggested that Fs-8-ba2, an acidic polysaccharide, could be of potential benefits in the treatment of the complement-mediated diseases.

Homogalacturonans from Preinfused Green Tea: Structural Characterization and Anticomplementary Activity of Their Sulfated Derivatives

Two homogeneous water-soluble polysaccharides (TPSR4-2B and TPSR4-2C) were obtained from preinfused green tea. Their average molecular weights were estimated to be 41 kDa and 28 kDa, respectively. A combination of composition, methylation, and configuration analysis, as well as NMR spectroscopy, indicated that both TPSR4-2B and TPSR4-2C were poly-(1-4)-α-d-galactopyranosyluronic acid in which 30.5 ± 0.3% and 28.3 ± 0.5%, respectively, of uronic acid existed as methyl ester. Two sulfated derivatives (Sul-R4-2B and Sul-R4-2C) from TPSR4-2B and TPSR4-2C were prepared after sulfation with a 2:1 chlorosulfonic acid-pyridine ratio. The anticomplementary assay showed that Sul-R4-2B and Sul-R4-2C demonstrated a stronger inhibitory effect on the complement activation through the classic pathway, compared to that of heparin. Preliminary mechanism studies by using complement component depleted-sera indicated that both Sul-R4-2B and Sul-R4-2C selectively interact with C1q, C1r, C1s, C2, C5, and C9 but not with C3 and C4. The relationship between DS and the anticomplementary activity of sulfated derivatives of homogalacturonans showed that low sulfated derivatives of homogalacturonans also exhibited potent anticomplementary effect, which might greatly reduce the side effects related to heparin and oversulfated chondroitin sulfate, such as anticoagulant activity and allergic-type reaction. These results suggested that sulfated derivatives of homogalacturonans might be promising drug candidates for therapeutic complement inhibition.

Anti-complementary Ginsenosides Isolated from Processed Ginseng

As part of an ongoing search for immunomodulatory components aimed at the anti-complementary effect, ginsenosides isolated from processed ginseng were found to have inhibitory activity on complement activation through classical pathways. Activity-guided fractionation was used to isolate four ginsenosides, namely ginsenoside Rg₆, F₄, Rk₃, and Rh₄. Ginsenoside Rk₃ and Rh₄ had a 3 fold higher inhibition activity than rosmarinic acid which was used as a positive control while ginsenoside Rg₆ and F₄ showed only mild effects similar to that of the positive control. The results suggest that the activity of the corresponding ginsenosides may be increased by the glycosyl moiety at the C₆ position rather than the double bond conformation at C₂₀, and ginsenoside Rk₃ and Rh₄ could have a role in treating inflammatory diseases.

A protein-bound polysaccharide from the stem bark of Eucommia ulmoides and its anti-complementary effect

Bioactivity-guided fractionation of a hot-water extract from the stem bark of Eucommia ulmoides led to the isolation of a homogeneous polysaccharide EWDS-2, which was identified as a highly branched protein-bound polysaccharide with average molecular weight between 1000 and 2000 kDa, composed of Glc, Gal, Ara, and Rha in the ratio of 2.2:1.0:0.4:0.2, along with traces of Man and 6.55% of protein. The main linkages of the residues of EWDS-2 include terminal, 1,3-linked, 1,4-linked, 1,2,6-linked, 1,3,6-linked Glc; 1,6-linked, 1,2,6-linked, 1,3,4-linked, 1,4,6-linked Gal; 1,5-linked, 1,3,5-linked Ara; terminal and 1,2,5-linked Rha. The bioassay revealed that EWDS-2 inhibits complement activation on both the classic and alternative pathways with CH 50 and AP 50 values of 282 ± 11 μg/mL and 144 ± 17 μg/mL, respectively. Preliminary mechanism studies indicate that EWDS-2 inhibits the activation of the complement system by interacting with C1q, C1r, C1s, C2, C3, C4, C5, and C9. The results suggested that EWDS-2 could be valuable for the treatment of diseases associated with the excessive activation of the complement system.

Effects of PspA and antibodies to PspA on activation and deposition of complement on the pneumococcal surface.

Streptococcus pneumoniae infection is a frequent cause of pneumonia, otitis media, meningitis, and septicemia. Pneumococcal surface protein A (PspA) is an important virulence factor on the pathogen surface, and it is known to interfere with complement activation. In this study, flow cytometry was used to study the effects of PspA and antibodies to PspA on the deposition of complement C3 on the surface of a capsular type 3 strain, WU2, and its PspA- mutant, JY1119. Using naive mouse serum as a complement source, measurable deposition of C3 was observed within 4 min on PspA- pneumococci, and the amount of surface-bound C3 accumulated rapidly as the amount of serum was increased. In contrast, very little C3 was deposited on the PspA+ strain. In nonimmune mouse serum, the classical pathway was the dominant activation pathway triggered by PspA- pneumococci. Accordingly, EGTA blocked almost all of the complement activation. Moreover, a significant amount of C3 was still deposited on the PspA- strain when serum from factor B-deficient mice was used. This deposition was not observed on the PspA+ pneumococci, indicating that PspA may inhibit complement deposition via the classical pathway. Furthermore, under the conditions we tested, PspA also inhibited C3 deposition when the classical pathway was initiated by antibodies to capsular polysaccharide. Antibodies to PspA could overcome the anticomplementary effect of PspA, allowing for increased complement activation and C3 deposition onto PspA+ bacteria.

Influence of the electric charge of the antigen and the immune complex (IC) lattice on the IC activation of human complement.

In order to understand the mechanism of complement (C) activation by immune complexes (ICs), the anti-complementary effect of ICs containing cationized antigens was compared in vitro to that using ICs formed by native antigens. ICs were prepared with affinity-purified rabbit polyclonal IgG antibovine serum albumin (BSA) antibody and either native BSA (isoelectric point 4.2) or BSA rendered cationic by treatment with ethylenediamine (isoelectric point 9.4). Native and cationized antigens were characterized by isoelectric focusing. ICs containing anti-BSA IgG or F(ab')2, formed either at equivalence or in excess of native or cationized antigen, were submitted to ultracentrifugation in a sucrose gradient for mesh size determination. The anti-complementary effect of ICs was evaluated by kinetic determination of haemolytic activity of human serum on haemolysin-sensitized sheep red blood cells. In conditions of antigen excess, the ICs formed by cationized BSA were significantly more efficient in activating human complement than those formed by native antigen. This higher activity was dependent on cationized antigen complexed with complete antibody molecules, as non-complexed cationized BSA or ICs prepared with F(ab')2 fragments were inactive under the same experimental conditions. Furthermore, this difference did not depend on the mesh size of the immune complexes. Our results suggest that the balance between antigen, antibody and C may be of importance in vivo for the onset and course of infections and other pathological processes involving IC formation. ICs containing cationized antigens should be proven of value in experimental models for studies on the regulation of C activation.

Effect of sodium nitroprusside on complement activation induced by cardiopulmonary bypass: A clinical and experimental study

Complement activation and leukocyte stimulation were prospectively studied during and after cardiopulmonary bypass in 16 children receiving sodium nitroprusside—a nitrovasodilator releasing nitric oxide—for vasodilation during the cooling and rewarming periods of extracorporeal circulation. Results were compared with those in 29 patients who were not treated with sodium nitroprusside during the operation. Patients treated with sodium nitroprusside had significantly less C3 conversion during cardiopulmonary bypass as measured by the ratio C3d/C3 (p < 0.05) and significantly less C5a liberation immediately after cardiopulmonary bypass (p < 0.005) than patients not treated with sodium nitroprusside. C4 was not overtly consumed in our series. Leukocyte count during the rewarming period of cardiopulmonary bypass, but not leukocyte elastase release during cardiopulmonary bypass, was significantly reduced in patients treated with sodium nitroprusside (p < 0.05). In vitro experiments were conducted to analyze the effect of sodium nitroprusside on complement hemolytic activity initiated by the classic and the alternate pathways and on zymosan-induced C3 conversion by the activation of the alternate pathway. The in vitro experiments clearly demonstrate inhibition of complement hemolytic activity by sodium nitroprusside in the sera tested. The 50% inhibitory concentration of sodium nitroprusside on the available complement hemolytic activity was less through the alternate pathway than through the classic one (4.2 ± 0.8 mmol/L and 14.0 ± 2.88 mmol/L, respectively). The decrease of complement hemolytic activity measured was dose-dependent and was enhanced by the sodium nitroprusside preincubation of the sera tested. This effect was related to the duration of preincubation. Sodium nitroprusside photodegradation (enhancing nitric oxide release) increased the anticomplementary effect of the drug, reducing the 50% inhibitory concentration on complement hemolytic activity to 0.24 to 0.02 mmol/L for the alternate pathway and 2.74 to 0.3 mmol/L for the classic pathway. The zymosan-induced C3 conversion was inhibited by sodium nitroprusside. Nitroglycerin and isosorbide dinitrate (other nitric oxide donors) had in vitro effects on complement hemolytic activity similar to those of nonphotodegraded sodium nitroprusside at similar concentrations (1 mmol/L). Our results suggest that sodium nitroprusside, both in vitro and in vivo, has an inhibiting effect on complement activation initiated by both classic and alternate pathways and that this effect is mediated by nitric oxide release from sodium nitroprusside. This is the first report on the anticomplementary effect of sodium nitroprusside by nitric oxide release. (J T HORAC C ARDIOVASC S URG 1996;111:882-92)

Anti-complementary activity of Crataegus sinaica.

The 80% and 70% acetone extracts from fruits and leaves of Crataegus sinaica Boiss (Rosaceae) and the ethyl acetate-, butanol-, and water-fractions obtained from these initial extracts as well as the isolated compounds, quercetin (1) (1), hyperoside (quercetin 3-O-galactoside) (2) (2), rutin (quercetin 3-O-rutinoside) (3) (2), vitexin (4) (1), rhamnosylvitexin (5) (3), monoacetylrhamnosylvitexin (6) (3), epicatechin (7) (4), procyanidin B-5 (8) (4), proanthocyanidin A-2 (9) (5), procyanidin B-2 (10) (4), and procyanidin C-1 (11) (4), were tested for their influence on the classical (CP) and alternative (AP) pathways of complement-mediated hemolysis. All extracts and fractions showed a strong anti-complementary effect in a dose-dependent way which was more pronounced on the CP than on the AP. The results indicated that the pure proanthocyanidins were active on the CP. Procyanidin C-1 and proanthocyanidin A-2 were the most active on the CP and also showed activity on AP, whereas the flavonoids isolated were generally less active. However, rutin, showed a strong activity, quercetin and rhamnosylvitexin a moderate activity on the CP. This is the first report on the chemical constituents and complement-modulating activity of C. sinaica and on the occurrence of proanthocyanidin A-2 (9) in hawthorn.

Immunologically active metallic ion-containing polysaccharides of Achyrocline satureioides

Two homogeneous, metallic ion-containing pectic polysaccharides with mean M r s of 7600 and 15 000 were isolated from dried aerial parts of Achyrocline satureioides by anion exchange column chromatography on DEAE-Sepharose CL-6B and gel filtration column chromatography on Fractogel TSK HW-50 (S). The structures, as determined by methylation analysis, carboxyl reduction, and partial acid hydrolysis, were shown to be rhamnogalacturonans. Both pectins show a pronounced anticomplementary effect in vitro. The larger carbohydrate AS 4 of higher M r exerts anti-inflammatory activity and a strong enhancement of phagocytosis in vivo.

Immunologically active polysaccharides of Arnica montana cell cultures

From the nutrition medium of Arnica montana cell cultures two homogeneous polysaccharides, an acidic arabino-3,6-galactan-protein with mean M r of 100 000 and a neutral fucogalactoxyloglucan with mean M r of 22 500 have been isolated by DEAE-Sepharose CL-6B and Sephacryl S-400 column chromatography. Their structures were elucidated mainly by methylation analysis, partial acidic and enzymatic hydrolysis and 13C NMR spectroscopy. The fucogalactoxyloglucan shows a pronounced enhancement of phagocytosis in vivo. The arabino-3,6-galactan-protein displays a strong anticomplementary effect and stimulates macrophages to excrete the tumour necrosis factor (TNF α).

House dust allergen activates the classical complement pathway in mouse serum

A house dust fraction was tested for complement activation in mouse serum using a microtitre complement fixation assay. It was observed that the preparation was a potent activator of the classical, but not of the alternative pathway suggesting an analogy with the complement activation in human serum. The activation showed similarity with that by classical complement activators such as aggregated IgG, DNA, lipopolysaccharide (LPS), but some discrepancy with mite allergen was observed. The contamination of the preparation with LPS was negligible and could not account for the anticomplementary effect. The role of DNA fragments in the activation of mouse complement by the house dust fraction is discussed. Our results suggest that the mouse is suited to study the role of complement activation by house dust constituents in the induction of the IgE response.

Differences in carbohydrate specificities and complement-activating capacity of guinea pig and human antibodies to neuraminidase-treated autologous erythrocytes

Guinea pig erythrocytes desialated by treatment with neuraminidase from Vibrio cholerae were lyzed in autologous serum through a natural-antibody-dependent activation of the classical complement pathway. Lysis was inhibited when mannose, glucose, galactose or N-acetyl-glucosamine was added to the incubation mixture. Methyl-α- or -β- d-galactopyranosides were poorly effective and N-acetyl - d-galactosamine was not effective at all. Inhibition of lysis by the carbohydrates was due neither to an anti-complementary effect nor to a modification of the osmotic pressure since: (a) they did not alter the total complement haemolytic activity of guinea pig serum, and (b) they did not inhibit lysis of desialated guinea pig erythrocytes in human serum through activation of the alternative complement pathway. The presence of mannose, glucose, galactose or N-acetyl-glucosamine in the incubation mixture resulted in an impaired fixation of natural auto-antibodies on antigenic sites, namely the T-antigen (Thomsen-Friedenreich), which were unmasked following membrane sialic acid removal. When tested under the same conditions, only small percentage of the normal human population showed the phenomenon of lysis of desialated erythrocytes in autologous serum. Lysis was not due to a particular susceptibility of erythrocytes from these individuals to complement-mediated lysis but to the presence in their serum of complement-activating anti-T antibodies. As expected, the activity of human anti-T antibodies as inhibited by galactose and N-acetyl-galactosamine, which are the immunodominant sugars of the human T-antigen. Mannose and glucose had no effect, and methyl-α- or -β- d-galactopyranosides were almost as effective as galactose. The heterogeneity of the human population with regard to the complement-activating capacity of anti-T antibodies could be of significance for the individual response of the host to an infection by a neuraminidase-producing microorganism. That the immunodominant sugars of the T-antigen were different between humans and guinea pigs was further assessed by absorption experiments. We have demonstrated that guinea pig anti-T antibodies were not removed during contact with desialated human red cells which do not have the mannose specificity, whereas human antibodies were almost entirely retained on desialated guinea pig red cells which, beside mannose, express galactose. These results also suggest that guinea pig antibodies are mostly directed towards mannose and glucose.

Hyaluronic acid-complement interactions—I. Reversible heat-induced anticomplementary activity

The in vitro interaction of hyaluronic acid (HA) with complement (C) classical-pathway activity has been investigated. It was found that native HA, even at a high concn (>3 mg/ml), has a relatively weak anticomplementary activity. However, we report here that native HA can be reversibly altered by heat treatment such that C-inhibitory properties are manifested. We have determined in this study that a potent C-inhibitory activity can be obtained if HA solutions are thermally treated (100°C), and stabilized by prompt freezing with prompt thawing just prior to the interaction with human serum complement. Several investigators have proposed that the intermolecular-associated strands of HA undergo a reversible decoupling upon thermal treatment and this decoupled state of HA can be semi-stabilized by quickly cooling the sample. This heat-treated HA strongly inhibits Cl as well as classical-pathway-mediated C3 conversion. However, if heat-treated HA samples are not stabilized but, rather, slowly cooled after heating or if heated HA samples are snapfrozen and then slowly thawed, the anticomplementary activity is gradually lost. Interestingly, the activity for this same sample can be regenerated by retreatment of the same sample with heat followed by low-temp stabilization, indicating the reversibility of the physical state of HA responsible for the anticomplementary effect. Since no detectable molecular degradation of thermally-treated HA was found, it was assumed that a heat-induced physical transition of HA (decoupled state) was responsible for the C-inhibitory effect.

Complement inhibitors in tears of different species

Tears of various species were investigated for the presence of inhibitors of the complement system. Rat and mouse tears contained strong anti-complementary activity, whereas goat, guinea pig, rabbit and rhesus monkey gave approximately the same inhibition as human tears. The chicken and cat only contained weak anti-complementary activity. Further analysis of the complement inhibitors in rabbit tears by gel-filtration and SDS-PAGE suggests that a small tear protein (approximately 20 000 daltons) may be involved in the anti-complementary effect in this species. Studies concerning the mechanism of inhibition in rabbit tears show that the complement cascade is inhibited after the EAC14 intermediate has been formed. The fact that various species were shown to have complement inhibitors in their tear film now enables the investigation of the physiological role of these factors.

Circulating immune complexes in rheumatoid arthritis with extra-articular manifestations.

Circulating immune complexes (CIC) and complement C4, C3 and CH50 levels in serum were monitored during 6-30 months in 10 patients with rheumatoid arthritis and extra-articular manifestations (EM). A total of 58 observations were made, 17 at times when new EM emerged, 41 at times when the patients were in a steady state. CIC were demonstrated by two methods, viz. a complement consumption test (CCT) and a polyethyleneglycol (PEG) precipitation assay. The precipitates were analysed for their content of IgG, IgM and IgA. The CCT titre decreased significantly at the time of a new EM, whereas PEG precipitates were found most often at this time. Two types of precipitate could be demonstrated. One consisted of IgG only, which was found most often when the patients were in a steady state. The other one was composed of IgG and other immunoglobulins, most often IgA. The latter type was found most often at the time when the patients developed new EM. Subnormal serum complement levels were demonstrated frequently. The level of C4 was significantly lower at the time of a new EM, compared with the level of patients with RA but without EM. The decrease in anticomplementary effect and the signs of complement activation suggest that the qualitative and quantitative changes in CIC observed at the time of new EM were the cause rather than the consequence of the clinical manifestations.

Inhibition of hemolytic complement activity by lactoferrin in tears

As previously reported human tears contain an anticomplementary factor capable of inhibiting total hemolytic complement activity in human tears. In order to elucidate the nature of this anticomplementary effect several techniques were used. Partial isolation of the anticomplementary factor in human tears by sucrose gradient ultracentrifugation and immunization of rabbits with the isolated fraction yielded an antiserum with a specificity for lactoferrin. The sedimentation profile of a major part of the anticomplementary effect in human tears coincided with that of lactoferrin. Further evidence that the anticomplementary activity was associated with lactoferrin was obtained by isolating lactoferrin from human tears by anion exchange chromatography. This resulted in an isolated fraction, containing anticomplementary activity, showing one band on SDS-polyacrylamide gel electrophoresis and which was identified as lactoferrin by immunochemical means. At a concentration of 4·8 μg/ml, isolated tear lactoferrin, could inhibit 50% of the hemolytic complement activity present in diluted human serum (containing 1·5 total hemolytic complement units). These findings thus show that a major part of the anticomplementary effect present in human tears is associated with lactoferrin. Ths suggests that lactoferrin, besides its known antibacterial properties may also have an anti-inflammatory function in preventing activation of the complement system on the external surface of the eye.

Different virus antibodies in serum and cerebrospinal fluid of patients suffering from subacute sclerosing panencephalitis

Complement fixing (CF) antibody titers to measles, parainfluenza (PI) types I and 3, mumps, herpes type 1, and cytomegalovirus (CMV) in serum and cerebrospinal fluid (CSF) of 33 patients with subacute sclerosing panencephalitis (SSPE) were evaluated. Results were analyzed in comparison to 11 patients with neurological diseases other than SSPE and 7 normal subjects. All SSPE patients had elevated serum and CSF measles antibody titers. The number of SSPE patients manifesting elevated titers other than measles did not reach statistical significance when compared to controls, except for PI type 1. This suggests a possible dual infection with measles and PI in SSPE. The anticomplementary effect detected in the serum and CSF of some patients indirectly suggests the presence of immune complexes.

THE IMMUNODEPRESSIVE EFFECT OF HUMAN GLUCOPROTEINS AND THEIR POSSIBLE ROLE IN THE NONREJECTION PROCESS DURING PREGNANCY

Human chorionic gonadotrophin (HCG) and human chorionic somatomammotrophin (HCS) were shown to suppress the proliferative T and B cell response induced by different mitogens in human and mouse lymphocytes. Thyroid stimulating hormone (TSH), sharing the alpha-chain subunit with HCG was devoid of effect suggesting that the immunosuppressive entity is localized within the beta-chain subunit. Human growth hormone (HGH) which is partly biologically cross-reactive with HCS did not impair mitogen responsiveness. HCG was also able to inhibit the differentiation of cells since the induction of antibody-formation was depressed. Expression of plaque forming cells was also reduced by addition of HCG directly in the PFC assay possibly reflecting the anti-complementary effect of this hormone, since cell mediated lysis of target cells by Con A activated lymphocytes, which is not complement-dependent, was unaffected by adding HCG in the assay system.