Diagnostic relevance of simultaneous testing for Chlamydia trachomatis and Neisseria gonorrhoeae.

BACKGROUND: The prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in a Swiss cohort among individuals consulting for screening or symptomatic reasons is not very well known. METHODS: Between January 2009 and January 2010, diagnostic samples referred to us to test for either CT or NG or both were simultaneously analysed for both infections. Testing was performed using the commercial m2000sp and m2000rt devices from Abbott Diagnostics involving automated DNA extraction and semi-quantitative real-time polymerase chain reaction (PCR), respectively. RESULTS: A total of 9,245 individuals (8,009 female, 1,236 male) were tested. CT alone was found in 318 (3.97%) samples from female patients and NG infections were found in 5 (0.06%) of the female samples. Six (0.08%) women had both CT and NG infections. The numbers for males were 72 (5.83%) for CT alone, 18 (1.14%) for NG alone and 8 (0.65%) for coincident infections. Among women, a selective testing approach in which only the presence of CT was investigated missed six NG cases (0.07% prevalence, 54.55% of all NG-positive women) and the request to test only for NG missed two CT cases (0.02% prevalence, 0.62% of all CT-positive women). For the male samples, one NG case (0.08% prevalence, 3.85% of all NG-positive men) was missed when only CT was requested and three CT cases (0.24% prevalence, 3.75% of all CT-positive men) were overlooked when only NG testing was requested. CONCLUSION: A sizeable number (12) of CT and NG cases is missed by physician-referred testing for only one of the two pathogens.

Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q.

A sensitive and reproducible procedure for the detection of soluble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled C1q is reacted with sera containing immune complexes. Separation of free from complex bound [(125)I]C1q is achieved by selective precipitation with polyethylene glycol (PEG). The method is based on both the large molecular size and the C1q-binding property characterizing immune complexes. The minimal amount of aggregated immunoglobulins thus detected is about 10 mug and that of soluble human IgG-anti-IgG complexes is about 3 mug of complexed antibody. Some immune complexes formed in large antigen excess (Ag(2)Ab) can still be detected by this radiolabeled C1q binding assay. The specificity of the radiolabeled C1q binding test was documented by the inability of antigen-F(ab')(2) antibody complexes to lead to a precipitation of [(125)I]C1q in PEG. In a second step, this radiolabeled C1q binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes.Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the hepatitis B antigen (HB-Ag). Significantly increased [(125)I]-C1q binding values were observed in 52 sera from SLE patients when compared to values obtained with healthy blood donors (P<0.001). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [(125)I]C1q binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [(125)I]C1q percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [(125)I]C1q. The results were also used for a correlative study of [(125)I]C1q binding to IgG levels in the sera but increased [(125)I]C1q binding could not be attributed to high serum IgG levels which are likely to account for gammaglobulin aggregates. These examples suggest the utility of the radiolabeled C1q binding assay for the evaluation of immune complex diseases in human pathology.

Circulating complement breakdown products in patients with rheumatoid arthritis. Correlation between plasma C3d, circulating immune complexes, and clinical activity.

Quantitative determination of the small C3 breakdown product, C3d, was used to investigate complement activation in 45 plasma samples from 30 patients with rheumatoid arthritis (RA). The mean plasma C3e level in these samples (3.0 +/- 1.3 mg/100 ml) was significantly increased (P less than 0.001) as compared to patients with degenerative joint disease (0.9 +/- 0.4 mg/100 ml) and healthy blood donors (0.8 +/- 0.5 mg/100 ml). C3d levels were increased by more than s SD in 79% of RA samples. Plasma C3d levels were compared with C3d concentrations in synovial fluid. In most RA patients, the C3d levels were higher in synovial fluid than in plasma. A very significant correlation between plasma C3d levels and circulating immune complexes, as measured by determination of Clq binding activity (Clq BA), was observed (P less than 0.001). C3d levels were more elevated in RA patients with extra-articular disease manifestations (3.8 +/- 1.2 mg/100 ml) as compared to patients with joint disease alone (2.2 +/- 1.0 mg/100 ml). C3d levels and Clq BA were also significantly correlated (P less than 0.001) with the RA disease activity expressed by an index derived from sedimentation rate, joint score, and duration of morning stiffness. A close relationship between C3d levels, Clq BA, and the clinical activity further appeared during follow-up studies. The present observations suggest that a parallel but rather independent activation of the complement system may be induced by immune complexes in circulating blood and in the joint spaces during the course of rheumatoid arthritis.

Histoblood groups other than HLA in organ transplantation.

Immunological matching of a living related donor and recipient of an allograft is precise, but for cadaver organs matching is controversial, including at least detection of specific sensitization in the recipient against the donor, especially for HLA-DR. With the publication of some cases of ABO histoblood group incompatible transplantations with favorable outcomes, transplantation immunologists now focus on many of the 29 International Society of Blood Transfusion-approved histoblood group systems. So far, research lags behind knowledge about which system occurs in which organ, but modern molecular biology tests, like basic local alignment search tools (BLAST) and the recent inclusion of some systems into the CD classification, make possible the tracking of some histoblood group epitopes to specific tissue components. We have conducted such a search. With respect to tissue distribution, mRNA transcripts, and expressed sequence tags (EST), we observed a huge variety of distribution patterns. The total number of EST in the embryo pool was 752,991 and in the adult pool 1,227,835. Representative results were described for umbilical cord, bone marrow, peripheral stem cells, the nervous system, and the embryo. The ABO histoblood group systems maintain high priority for matching, because of the occurrence of naturally occurring anti-A/B antibodies. Substantial progress has been made in monitoring their levels and immunoglobulin isotypes in recipients, which, beyond hemagglutination, can now be quantitated using ELISA or cytofluorometry. A picture of ever-improving compatibility matching in solid organ and stem cell transplantation beyond mere HLA typing is the consequence.

Autoantibodies with antilipoprotein specificity and hypolipoproteinemia in patients with cancer.

Sera from 151 patients with a variety of cancers were screened for antibody-like activity against lipoproteins. Eighteen % of the sera exhibited activity against autologous and homologous high-density lipoproteins and 3% exhibited activity autologous and homologous low-density lipoprotiens. Antibody-like binding was proven by its restriction to the Fab fragment of IgG. The reactive part of the lipoprotein molecule was shown to be the appoprotein. Quantiation of the serum lipoproteins indicated that thehigh-density lipoprotien concentration in the sera of cancer patients was significantly lower (psmaller than 0.01) when antibody was present. These observation suggest that autoimmune mechanisms may be responsible for the decreased high-density lipoprotein serum levels in some patients with cancer.

Soluble type A substance in fresh-frozen plasma as a function of ABO and Secretor genotypes and Lewis phenotype.

Soluble ABO blood group substance (SAS) in fresh-frozen plasma (FFP) and its cognate alloantibody titer reduction capacity (TRC) are not considered when prescribing this product for plasma exchange (PEX) therapy of ABO incompatible transplant recipients. SAS was quantified in 250 single FFPs using ELISA. Total and IgG class-specific anti-A TRCs of FFPs were measured using a microhemagglutination inhibition assay. SAS level depended not only on the A subtype (p < 0.0001) and the Secretor status (p < 0.0001), but also on the expression of ALe(b) in A1 secretors (p < 0.0001). The variation was as great as 137.6 arbitrary units (aU) for 14 A1 Le(a-b-) secretors and 1.2 aU for 6 A2 non-secretors. Homozygous expression of the A1, A2 and Secretor alleles did not increase SAS levels. Only total anti-A TRC, but not IgG class-specific TRC depended on the detected SAS level (r = 0.566, p = 0.0003).

Recurrent meningitis in a patient with congenital deficiency of the C9 component of complement. First case of C9 deficiency in Europe.

We describe the first cases, to our knowledge, of C9 deficiency in Europe that were detected in a Swiss family, of which two members--one with a complete deficiency and the other with approximately half-normal C9 levels--experienced bacterial meningitis. The index patient, a 56-year-old white man with a history of purulent meningitis at the age of 23 years, presented with an acute meningococcal meningitis. No impairment of cellular immunity or immunoglobulin deficiency could be found. Complement assays showed a complete deficiency of the C9 component, while the other individual component levels were normal and the hemolytic activity (measured using the CH50 assay) was only slightly reduced. A family study revealed complete C9 deficiency in the patient's healthy brother and half-normal C9 concentrations in his sister, his son (who also had experienced an episode of bacterial meningitis), and his niece, consistent with an inherited C9 deficiency. This first case of recurrent meningitis in a white patient with complete C9 deficiency suggests that this complement defect may also be a risk factor for bacterial, especially neisserial, infections.

Immunoglobulin-mediated shifting of immune complexes to increased complement-dependent solubility and immunoadherence.

The effect of a monomeric polyclonal polyspecific IgG preparation (mIgG) for i.v. use on the capacity of fresh normal human serum (NHS) to inhibit precipitation of immune complexes of tracer-labeled bovine serum albumin (BSA) and anti-BSA (aBSA) rabbit antibody was investigated. Relative to heat-inactivated serum which showed no capacity to inhibit immune complex precipitation (CIICP), fresh NHS at a final dilution of 1:3 or 1:2 showed a 12 and 46% CIICP, respectively, with a BSA:aBSA ratio at equivalence. Addition of incremental amounts of mIgG dose-dependently enhanced CIICP of NHS to reach 63 and 90%, respectively, at a concn of 13.0 mg/ml mIgG. Human serum albumin instead of mIgG had no influence on CIICP of NHS indicating that the phenomenon was not dependent on non-specific protein-protein interactions. Although minimal amounts of BSA cross-reactivity could be demonstrated in mIgG, the extent of this activity was too small to explain the CIICP-supporting effect of mIgG as determined by comparing the effect of mIgG and aBSA serum on CIICP of fresh serum. Furthermore, absorption of mIgG on BSA-Sepharose did not lead to impairment of its CIICP-supporting effect. A direct binding of tritium-labeled mIgG (3H-mIgG) to either insoluble BSA:aBSA complexes or latex-bound IgG (IgG-latex) was found. Incubation of 2.7 micrograms 3H-mIgG with 90 micrograms IgG-latex resulted in a specific binding of 5.2% of the labeled compound. Such binding could be inhibited by unlabeled mIgG. Binding of mIgG was mediated through the Fab as well as the Fc part of the molecules: the 3H-Fc as well as the 3H-Fab fragment of mIgG bound to IgG-latex. The extent of binding of Fc was more than twice that of Fab and amounted to 70-90% of the binding found with intact mIgG. In an immune adherence hemagglutination system that depends on the interaction of complement-reacted immune complexes with C3b receptor-bearing erythrocytes, evidence was obtained that the mIgG preparation facilitated fixation of C3b to performed BSA:aBSA complexes. Addition of 1.45 mg/ml mIgG reduced the quantity of antigen-complexed C3b-bearing aBSA antibodies required to show a given agglutination by a factor of 3-4. We conclude that the facilitating effect of high doses of mIgG on complement-dependent CIICP of NHS and on immune adherence hemagglutination is the amplifying effect of complement after an initial interaction of antigen-nonspecific polyclonal polyspecific IgG with antigen-reacted antibody.

Use of epoetin alfa in autologous blood donation programs for patients scheduled for elective cardiac surgery.

The optimum dosage of subcutaneous (s.c.) epoetin alfa was assessed in a double-blind study in 31 patients scheduled for cardiac surgery. Patients received a total of four doses of either epoetin alfa 150 IU/kg (n = 11), epoetin alfa 300 IU/kg (n = 10), or placebo (n = 10) administered as single s.c. injections at weekly intervals starting 23 days prior to surgery. AB was collected with isovolemic replacement prior to each of the first three doses of medication. During the AB donation period, Hb levels decreased significantly (P < .05) from baseline to surgery in the placebo group (16.5%), compared with no significant decrease in either of the epoetin alfa groups (8.1% and 9.7% in the 150 IU/kg and 300 IU/kg groups, respectively). In addition, the difference between groups with regard to the decrease in Hb level reached statistical significance (P < .05) for the 150 IU/kg group versus placebo. Epoetin alfa treatment was also associated with significantly higher reticulocyte counts and serum erythropoietin levels in the preoperative period compared with placebo.

Development of an ABO-ELISA for the quantitation of human blood group anti-A and anti-B IgM and IgG antibodies.

An indirect ELISA system was designed for quantitation of human blood group A and B IgM and IgG antibodies. The capturing antigens are blood group substance A or B used to sensitize polystyrol microtiter plates. Bound anti-A or anti-B antibodies are revealed either directly, by development with polyclonal anti-human immunoglobulin class-specific conjugate or with more avid mouse monoclonal anti-human isotype antibodies revealed in turn by goat anti-mouse conjugate. Reproducibly, 100 ng specific anti-A IgG provided for a significant above-background signal of 0.2 at OD405 and 15 serum samples had a mean content of 3.98 +/- 8.74 micrograms (mean +/- 2 SD) (range: 0.305-12.62) of specific anti-A IgG/g total IgG. Thus one molecule specific anti-A IgG is found per 7.9 X 10(4)-3.2 X 10(6) total IgG molecules. Statistical correlations were significant between anti-A IgG levels and agglutination titer (P less than 0.05) but non-significant when the specific anti-A IgG levels of individual serum samples were compared to their total IgG content (P greater than 0.05). Dose-response signals were similar for anti-A and anti-B IgM antibodies. Reproducibility of the assay was excellent. Specificity was ascertained by various approaches involving development of primary antibodies with heterospecific antibody conjugate and adsorption of primary antibody from serum using A and B group erythrocytes or soluble A and B substances. Separation of IgM from IgG anti-A antibodies over sizing gel resulted in fractions that were immunosorbed by mouse monoclonal anti-human IgM and IgG respectively but not vice versa.

Development of a C1q-ABO-ELISA to measure C1q binding by human anti-A alloantibodies.

Little is known about the correlation between the amount of anti-A antibodies and the respective complement activating capacity. We have therefore developed a new ELISA procedure for the study of complement activation by anti-A antibodies bound to immobilized blood group substance A through the classical pathway. C1q binding capacity of anti-A was then compared to both anti-A immunoglobulin (Ig) isotype serum concentrations and to the hemolysing capacity of O type sera. We have demonstrated that sera with low anti-A IgG and IgM levels produced low C1q binding activity and no hemolysis of human A1 red blood cells (RBC), whereas higher anti-A Ig levels resulted in either weak or strong C1q binding capacity as well as weak or strong RBC hemolysis. A correlation of rs = 0.755 was observed between C1q-ABO-ELISA and hemolysin assay results, although only 58% of the O type sera containing C1q binding anti-A lysed A1 type RBC under the used conditions. The C1q-ABO-ELISA is therefore a more sensitive assay for detecting 'dangerous' O type donors for blood transfusion to A type recipients than screening tests for hemolytic anti-A or determination of anti-A Ig levels alone.

Successful management of a B-type cardiac allograft into an O-type man with 3(1/2)-year clinical follow-up.

BACKGROUND: In May 1997, a 19-year-old male patient of histo-blood group type O suffering from congenital end-stage heart failure accidentally received a cardiac allograft of type B and is still alive in fair condition. METHODS: In addition to conventional immunosuppressive therapy, plasma exchange (PEX), extracorporeal immunoabsorption (EIA), intravenous immunoglobulins (IVIG), and C1 inhibitor were used. RESULTS: Such treatment successfully reduced both IgM and IgG anti-B levels and complement hyperactivity and allowed to reach the state of accommodation without obvious signs of rejection. The patient has been surviving for 42 months; retransplantation with an O-type heart remained unnecessary. CONCLUSION: Humoral rejection has been avoided in this patient, with PEX, EIA, IVIG, and C1 inhibitor substantially contributing to this success. With future availability of such combined therapies, preferably before transplantation, vascular rejection events caused by preformed antibodies and complement (ABO mismatch or anti-HLA) could be prevented or treated.

In vitro evaluation of the efficacy and biocompatibility of new, synthetic ABO immunoabsorbents.

Synthetic ABO immunoabsorbents (known as Synsorbs) were in use for several years to specifically eliminate ABO antibodies from the patient's circulation before ABO-incompatible organ or bone marrow transplantation. Because Synsorbs are no longer available, we have developed new ABO immunoabsorbents. These substances, termed BioSorbents A and B, respectively, consist of synthetic A or B trisaccharides covalently coupled to macroporous glass beads via polyacrylamide. Here we report the evaluation of BioSorbents in regard to efficacy, specificity, and biocompatibility. Using a closed-circuit in vitro system, representing a 1:10-1:20 scale as compared with the immunoabsorption procedure with an adult patient, blood group O plasma was run through columns filled with ethylene oxide-sterilized BioSorbent. Hemagglutination was reduced by 4 titer steps after absorption, and anti-A and/or anti-B IgM/G/A, as measured by ABO ELISA, dropped by 85% or more, while no nonspecific absorption of immunoglobulins occurred. No significant changes could be observed for complement (C3, C4, and total hemolytic complement of the classical pathway) or for coagulation parameters (fibrinogen, prothrombin time, activated partial thromboplastin time). As monitored by immunoblotting, neither factor XII nor high molecular weight kininogen was cleaved. In addition, a monocyte phagocytosis inhibition test provided evidence that no significant aggregation of IgG had occurred during absorption. We conclude that BioSorbents A and B are efficient, specific, and biocompatible with human plasma.

Role of immune complexes in pathogenesis of renal disease.

When judged by histological criteria, kidney tissue is practically devoid of immune tissue; as yet a broad spectrum of immunological diseases are targeted at the kidneys, especially at the glomeruli. Glomerular epithelial cells exhibit immune protein receptors and hence could clear immune complexes decorated with complement from the circulation. Alternatively, circulating immune complexes could become trapped in the glomerular filter and start off inflammatory reactions. Anti-glomerular basement membrane antibody reacts with glomeruli and causes glomerulonephritis. The present text is an analysis of the impact of immune complex formation on renal pathology and contains retrospective clinical data of our own hospital obtained on 192 patients undergoing diagnostic renal biopsy.

Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT(1) antagonists.

BACKGROUND: Erythropoietin (Epo), a growth factor produced by the kidney, is important in heart failure patients to promote oxygen delivery to tissues. Seventy-two chronic heart failure (CHF) patients at our outpatient clinic were subjected to morning serum Epo-level measurements and classified according to NYHA criteria. RESULTS: Forty-eight patients of classes III and IV had a significantly elevated serum Epo-level of 42.9+/-40.3 mIU/ml (mean+/-1 S.D.) when compared to the mean level of 24 patients of classes I and II who had a normal range mean value of 13.4+/-6.2 mIU/ml (P<0.05). Patients on angiotensin-converting enzyme (ACE) inhibitors showed a trend towards lower serum Epo-levels compared to patients treated with angiotensin-II type-1 receptor antagonists (AT(1) antagonists) (levels: 33.3+/-35.6 mIU/ml and 43.6+/-38.1 mIU/ml). This trend did not, however, reach statistical significance (P=0.36). CONCLUSION: We suggest that a desirable Epo increase in class III and IV CHF patients could be achieved by either recombinant human Epo administration or, possibly, by appropriate selection of the concomitant medical therapy. A large prospective study shall investigate the possible advantage of AT(1) antagonists over ACE-inhibitors with regard to Epo effect.

Anti-Galalpha1-3Gal IgM/IgG antibody levels in infants: do they have a clinical relevance in pediatric xenotransplantation?

BACKGROUND: Anti-Galalpha1-3Gal antibodies (anti-Gal) compose a major obstacle to xenotransplantation. As it is known, there is an immunological window during which infants are thought to have no xenoreactive antibodies. Therefore, we were interested in investigating the occurrence of these antibodies in newborns and infants up to 2 years of age. METHODS: IgM/IgG isotypes of anti-Gal from 74 serum samples of 16 mothers, with the respective cord bloods, and 42 infants of 4 age groups (Group I: day 1-6 months, II: 7-12 months, III: 13-18 months, and IV: 19-24 months) were determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA). A synthetic Galalpha1-3Gal disaccharide-polyacrylamide glycoconjugate was used for coating and monoclonal antibodies were used for the detection of heavy chain isotypes. Antibody concentrations were referred to an internal standard and expressed as arbitrary ELISA units (U). Hemagglutination titers against rabbit erythrocytes (E(R)) were determined in addition. RESULTS: Maternal serum samples showed a wide interindividual variability (IgM: 87 +/- 33 U (mean +/- SD), IgG 59 +/- 39 U) whereas in cord blood no detectable IgM was seen in presence of IgG (52 +/- 34 U). From Group I to IV there was a gradual increase of anti-Gal IgM towards an average of 70% of the adult levels whereas IgG fell to an average of approximately 20% of cord blood levels. Hemagglutination titers followed an increasing tendency with cord blood starting from 1:16 and reaching 1:256 in Group IV. CONCLUSION: The humoral immune response to the Galalpha1-3Gal epitope (alpha-Gal) in infancy follows the generally known development of specific antibodies in humans.

New concepts in organ preservation.

Organ preservation between donor and recipient is an important link in a chain that ultimately should lead to long term survival of the recipient thanks to a well-preserved, functionally intact organ. The period of organ ischaemia outside the body is subject to a number of biochemical stress factors which become known in more detail as knowledge on biochemical and immunological mechanisms improves. Efficacy of preservation fluids hence reduction of ischaemia injury may become enhanced by such additives as ion channel blockers, enzyme inhibitors, haeme oxygenase modulators, endothelin-l-inhibitors, quenchers of free radicals and anti-apoptotic agents. Many of these compounds, albeit of great theoretical interest, have not (yet?) made their way into clinical practice. This contribution is a survey of some promising agents, concentration and physicochemical interactions of which are analysed in some detail.

Polyvalent immunoglobulins for prophylaxis of bacterial infections in patients following multiple trauma. A randomized, placebo-controlled study.

One hundred and fifty severely injured patients requiring long-term artificial ventilation were evaluated in a prospective, randomized, double blind study comparing the prophylactic effect of an intravenous immunoglobulin (Sandoglobulin; IGIV) against nosocomial infections with a placebo preparation. The groups were comparable in age, sex, injury pattern, and severity of the trauma. Seventy-six patients received 12 g of Sandoglobulin as a 3% solution on day 0, day 5 and day 12, i.e. a total of 36 g. Sandoglobulin significantly reduced the incidence of pneumonia (28 cases in the IGIV group, 43 cases in the placebo group, p = 0.0111). This resulted in a reduced therapeutic use of antibiotics. For the occurrence of sepsis (IGIV: 14 cases; placebo 19 cases) and other infections (IGIV: 11 cases; placebo: 10 cases) no significant differences were found. No side effects of the administration of IGIV were observed. IGIV prophylaxis neither reduced the overall death rate nor those deaths caused by infection. On day 5 after administration of the first 12 g of IGIV, the IgG serum concentrations were significantly higher in the Sandoglobulin group (8.41 +/- 1.96 mg/ml and 7.42 +/- 2.25 mg/ml respectively, p less than 0.001) whereas later serum samples showed no significant differences.

Adverse effects of intravenous immunoglobulin therapy.

A growing body of literature documents that intravenous immunoglobulin prophylaxis and therapy is becoming applied to a steadily growing list of new indications. Some of these new indications have led to the use of intravenous immunoglobulin therapy in doctors offices, far from the hospital environment. Being stable products purified from blood or plasma donations, intravenous immunoglobulins must be considered as biological products in addition to their status as pharmaceutical products. This makes the study of adverse reactions reach beyond a mere drug safety surveillance programme into the realms of good manufacturing procedures guaranteeing not only intravenous tolerance but also sterility with regard to transfusion transmitted agents. The initially perceived adverse effects, stemming from complement activating aggregated immunoglobulin G, had the effect of slowing down widespread introduction of intravenous immunoglobulin therapy in the late 1970s. These adverse effects have now been eliminated with amendment of the appropriate manufacturing steps. However, new adverse effects, such as hyperviscosity, aseptic meningitis or renal insufficiency, have been observed which can be assigned to certain comnpounds of intravenous immunoglobulin, to administration regimens or to special patient characteristics. Adverse effects can be divided into 3 types: immediate adverse effects (those that occur during the infusion, e.g. anaphylactoid reactions); delayed adverse effects (those that occur hours to days after initiation of the infusion, e.g. renal, pulmonary, dermatological adverse effects, hyperviscosity, aseptic meningitis, arthritis, cerebral infarction, haemolysis and leucopenia) and; late adverse effects (e.g. transmission of infectious agents). We conclude from our analysis, that in general, intravenous immunoglobulin may be considered a well tolerated medical agent provided the indication for use is chosen carefully and use is monitored by a physician familiar with contraindications, risks, adverse effects and their appropriate management.

Safety and side effects of i.v. immunoglobulin therapy.

The safety of i.v. immunoglobulin therapy, as compared to other therapeutic measures used in modern medicine today, is rather good. However, a number of side effects may become serious in patients at risk. Thanks to over 20 years of experience with i.v. immunoglobulins, we hope to soon be able to draw up a nearly complete list of potential side effects. In fact, knowledge of the possible side effects is essential when it comes to their prevention. The elderly, patients with kidney disease and arteriosclerotic patients, as well as IgA deficient recipients, are at risk, but may well receive i.v. immunoglobulins if certain prophylactic measures are taken or if the infusion speed and/or the total dosage given are properly adjusted. This article will deal with the major side effects of i.v. immunoglobulin therapy and their prevention.