Israel Medical Association Journal

Giant cell arteritis (GCA) is considered to be a T cell-dependent disease. Autoantibodies have not consistently been found in GCA. The exception is antiphospholipid antibodies (APLA), which were found in 30–80% of GCA cases. Recently, efforts have been made to seek autoantibodies in GCA using newer methods of detection: serological identification of antigens by recombinant cDNA expression cloning, and a proteomic approach. In these studies, lamin C (a nuclear envelope antigen) was recognized by antibodies in 32% of GCA sera and none of the controls. Other autoantigenic proteins were also identified: lamin A, vinculin (a cytoskeleton antigen), and annexin 5 (an endothelial protein). In a recent study, 92% of 36 patients with GCA and/or polymyalgia rheumatica (PMR) had autoantibodies to a human ferritin peptide (the heavy chain N-terminal); 89% had antibodies to bacterial ferritin peptide of Staphylococcus epidermidis. The significance of these findings needs to be studied further. GCA may be a part of the newly described ASIA syndrome (autoimmune syndrome induced by adjuvants). A recent study from Italy reported 10 cases of GCA/PMR within 3 months of influenza vaccination. These comprised 50% of all cases of GCA/PMR diagnosed during the 6 year period of the study. Another 11 cases of GCA following influenza vaccinations were reported. GCA pathogenesis involves all branches of the immune system, including antigen-presenting cells, T cells and B cells, and autoantibody formation is not uncommon. GCA etiology remains unknown, but may be associated with exposure to bacterial or viral antigens.  

Objective: To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia.

Methods: Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies binding to normal platelets in the presence or absence of the patient’s serum was studied by flow cytometry.

Results: Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation.

Conclusions: These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia. 

 Background: Human amnion membrane (HAM) was suggested to be a superior antigenic substrate for immunoblotting in detecting autoantibodies of autoimmune bullous skin diseases.

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris. 

 Background: The presence of anti-citrullinated peptide/protein antibody (ACPA) has a high specificity and predictive value for the development of rheumatoid arthritis (RA). Some studies have shown decreased titers of this antibody after treatment with infliximab.

Objectives: To assess the changes in ACPA titers in patients with RA after treatment with infliximab as a first biological agent, and to correlate these variations with non-infusion-related adverse effects.

Methods: In a prospective multicenter observational study involving 48 research centers, we assessed 139 patients with established moderate-to-severe RA diagnosed according to American College of Rheumatology criteria. Samples were collected before and 6–12 months after treatment.

Results: The mean age of the study patients was 50.6 years old, and 118 were female (84.9%). Statistically significant variations in ACPA titers were noted in 47 patients (before and after treatment) (P = 0.012). Overall, ACPA titers were decreased in 32 (65.3%) and increased in 15 (34.7%). No correlation was found between severe or mild adverse effects in patients presenting variations in ACPA titers.

Conclusions: The present study showed that infliximab affected ACPA titers, promoting mainly a decrease; however, this was not related to the occurrence of non-infusion-related adverse effects.

 

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism. 

 Anti-citrullinated peptide antibodies (ACPA) are detected in the sera of rheumatoid arthritis (RA) patients and have a profound role in diagnosis of the disease. In this review we discuss the different cohorts of RA patients in whom the presence, sensitivity and specificity of ACPA were evaluated. The significance of ACPA in the pathogenesis and prognosis RA is also interpreted. Recent advances in the understanding of molecular pathways involved in the pathogenesis of RA have led to the identification of novel biologic agents that are now widely used in patients with RA