Iranian journal of immunology
Volume:1 Issue: 2, Summer 2004

The subject of transplant immunosuppression has generated significant interest in recentyears. Excellent immunosuppression, advances in surgical technique, post-transplantation care, and infection control have resulted in excellent outcomes. There is widespread support for the notion that the fundamental objective in transplant immunology should be the achievement of specific graft tolerance. However, until this objective evolves into reality, investigators are in search of the “ideal immunosuppressant”, which should target predominantly the immune system with minimal consequences for other tissues and minimal metabolic, cardiovascular and renal complications. While immunosuppressants have been associated with a tremendous trade-off in terms of morbidity, new agents have provided the investigators with the opportunity to formulate strategies that employ combination therapies with the goal of decreasing doses of individual agents and minimizing their toxicities. Multiple small studies have addressed the issue of minimizing immunosuppressants, but there is a need for well-designed clinical trials which should evaluate protocols that will reduce acute rejection, as well as chronic allograft nephropathy. They should address methods to identify subsets of patients who would maximally benefit from avoidance or withdrawal of steroids or calcineurin inhibitors. Other promising areas of research include tolerance studies among the sensitized recipients, and development of optimal immunosuppression based on genotype. In general, future trials must include a more diverse population of recipients, particularly the immunologically high risk groups.

To compare immunogenicity of a recombinant hepatitisB (HB) vaccine in two groups of neonates born in two cities of Iran with different geographic and ethnic backgrounds. Ten micrograms of a recombinant HB vaccine was administered under field condition to Iranian healthy neonates at 0, 1.5 and 9 months intervals. The subjects consisted of two groups of 290 and 231neonates selected fromtwo cities located at north-west (Urmia) and south-east (Kerman) of Iran, respectively. The level of anti-HBs antibody was quantitated in serum 2-4 weeks after administration of the last vaccine dose, by sandwich ELISA. Ahigher seroprotection rate (anti-HBs> 10 IU/L) (98.3%vs. 96.1%) and significantly increased serumanti- HBs antibody titer (11869 vs. 6104 IU/L) (P<0.001) were induced in vaccinated neonates fromUrmia city, compared to those born in Kerman. These findings suggest contribution of ethnic and/or environmental factors in the antibody response to recombinant HB vaccine in human.

To investigate possible immunological humoral correlates innewly diagnosed adult-onset generalized tonic-clonic epilepsy among Iranian patients before and after sodiumvalproate treatment. Patients and 72 adult patients with newly diagnosed idiopathic generalized tonic-clonic epilepsy were recruited. Serum antinuclear antibodies (ANA), anti-cardiolipin antibodies (aCL), anti-dsDNAantibodies, total serumimmunoglobulins (IgM, IgG, IgA) and C3 and C4 complements were determined before and after 12 months of therapy with sodiumvalproate. Similar parameters were also measured in 32 age and sex-matched healthy volunteers. Patients group had a significantly greater level of IgG class aCL (30.6%versus 12.4%, P = 0.004) and anti-dsDNAantibodies (23.9%versus 0%, P = 0.001) when compared with healthy volunteers, however, ANAtitre was relatively the same in both groups. Sodiumvalproate significantly decreased anti-dsDNAantibodiles (P= 0.002), IgMconcentrations (P = 0.034), and increased the number of ANApositive patients (P = 0.002). Changes in serumlevel of autoantibodies in patients with new onset idiopathic generalized convulsion were found to be high. These abnormalities are associated with both seizure disorders per se and also antiepileptic drugs.We suggest that in epileptic patients with an autoimmune basis, administration of anti-epileptic drugs having modulatory effects on immune systemshould be considered.

The clinical value of IgG anticardiolipin antibody in patients with Behçet''s disease with or without vascular thrombosis was evaluated. IgG isotype of anticardiolipin (aCL) antibody was assessed in 40 Behçet''s disease (BD) patients with venous or arterial thrombosis, 40 BD patients without venous or arterial thrombosis and 80 healthy subjects as controls. The levels of IgG aCL were determined by an indirect ELISAmethod. Color Doppler Sonography, Magnetic Resonance Imaging and conventional angiography were the procedures used for other clinical evaluations. Out of 40 patients with vascular thrombosis, 20(50%) were positive for low to moderate level of IgG aCL. In patients without thrombosis 22(55%) were positive for low to moderate level of IgG aCL while in none (0%) of the healthy subjects the IgGaCL was positive, neither low nor moderate. The number of patients with headache but having a normal cerebral magnetic resonance imaging (MRI), was higher in anticardiolipin positive patients without vascular thrombosis as compared to those with vascular thrombosis, (P = 0.001).Arthritis was noticed in both patents groups. 15% of aCL positive patients without thrombosis had arthritis as compared to none in aCL negative patients without thrombosis (P = 0.02). The results of this study indicate that although the frequency of IgG aCL was found to be higher in Iranian patients with BDin comparison with the previous reports, except in arthritis the observed elevated IgG aCL does not correlate with clinical disease manifestations, or vascular thrombotic complications.

Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgMisotype in blood, measured by a standardized ELISAis the most acceptable laboratory criteria. APS IgGisotype, particularly IgG2 subclass is more strongly associated with thrombosis. This study was done to determine the prevalence of IgG aCL and its subclasses in relation to APS symptoms, in a group of juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (SLE) patients. In this prospective study, 28 JRAand 16 SLE patients, aged 3-18 years, were enrolled. IgG aCLwas assayed by standard aCL ELISA. IgG subclasses were also assayed by ELISA on sera with medium to high titers of aCL.ACL assay was performed on at least two occasions for each patient, over 3-6 months period of follow up. 29%(8/28) of JRApatients and 44%(7/16) of SLE patients had aCL. Six of SLE patients displayed APS related manifestations: hemolytic anemia, thrombocytopenia, arterial occlusion, valvular heart disease, livedo reticularis and pulmonary hypertension, but none of them had persistant medium or high titer of aCL. The lack of association of high titer of aCL with APS related symptoms was observed in two patients. The IgG subclasses wereprimarily IgG1 and IgG3. The prevalence of IgG aCL in this group of pediatric SLE and JRAis not uncommon but it’s relation to clinical manifestations is not clear. IgG1 and IgG3 subclasses were not associated with thrombosis, which is in agreement with previous studies.

Pulmonary tuberculosis (PTB) has recently become a major problem indeveloped countries especially in immune compromised HIVinfected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis. In the present study the genotype frequencies of a number of polymorphic genes coding for cytokines or for cytokine receptors have been investigated in a case control study including a group of 40 Iranian PTB patients and 40 healthy individuals. The allelic polymorphism of cytokines SNPs were analyzed according to the protocols of the cytokine component designed for the 13th IHW by the Heidelberg University group. Using PCR-SSP method the following cytokine genes have been determined: IL-1 (T/C –889), IL-1 (C/T +3962), IL-1R (C/T pstI 1970), IL-1RA(T/C mspaI 1100), IL-4RA(G/A+1902), IL- 12 (C/A –1188), TGF- (C/T codon 10, G/Ccodon 25), TNF- (G/A –308, G/A –238), IL-2 (T/G –330 G/T +166), IL-4 (T/G –1098, T/C –590, T/C –33), IL-6 (G/C –174, G/A nt 560), IL-10 (G/A –1082, C/T –819, C/A –592). From IL-1R cluster (pro- inflammatory cytokines) a positive significant association was found at position pstI 1970 C/T polymorphismwhere theC allele was over presented in the PTBpatients (60% vs. 37.5%, P = 0.04).Asignificant negative association at codon 10 TGF- C/T polymorphism has also been shown in our patients, where the T allele was not detected in the patients but 10% of the control subjects expressed this allele (Fisher exact test, P = 0.05). At this codon allele T (Leucine substitution) is associated with high TGFproduction. For TNF an insignificant tendency was found at position -308 A/G polymorphismwhere theG allele carried by 80% of cases and 65% of controls (P = 0.07).At position -238 a negative association was found at the GApolymorphism(10% vs. 25%, P = 0.07). For IL-6 an insignificant positive association at position -174 C/G *Corresponding author: Dr. Ali Akbar Amirzargar, Department of Immunology, Immunogentic Laboratory, Medical School, Tehran University of Medical Sciences. e-mail: Amirzargar_Ali@yahoo.com Cytokine gene polymorphismin Pulmonary TBpolymorphism, G allele (57.5% vs. 37.5, P = 0.07) was found. At the other cytokine genes no specific association were found. In conclusion it is suggested that C allele at position pstI 1970 of IL-1 cluster increases and T allele at codon 10 of TGF- decreases in PTB patients.

Type 1 Diabetes (T1D) is a chronic and progressive autoimmune disorder.Cytokines play a critical role in the pathogenesis of T1D. IFN- polymorphism was investigated in T1D and compared with normal controls. Thirty patients suffering fromT1D and 40 normal controls were studied simultaneously using PCR technique. IFN- gene was evaluated at position 5’UTR +5644. There was a significant difference between patient and control groups in TT genotype (P<0.05). In this study, we found a negative association between IFN- gene at position 5’UTR +5644 and T1D in Iranian patients pointing to T allele as a protective factor against T1D.

Allergic rhinitis is one of the most common forms of allergic disordersaffecting children. The prevalence rate of allergic rhinitis differs among countries and even among regions within the same country. To determine the prevalence of childhood allergic rhinitis and the presence and significance of eosinophilia in nasal secretions. 4584 children aged 11-15 years-old of both sexes with allergic rhinitis were studied. The study was done during a four-season period. After physical examination of the nose, smear was taken from nasal secretions and it was stained. The results compared with nasal smears related to 340 healthy children controls. 445 cases (9.7%) were diagnosed as having allergic rhinitis, on the basis of clinical criteria. Significant nasal eosinophilia was present in 274 (62%) of children with allergic rhinitis. 226 students (5.8%) of Shiraz school children had proven or classic allergicrhinitis. Allergic rhinitis is one of the major health problems among children in Shiraz. Eosinophilia of nasal secretions had a diagnostic specificity of 96% and sensitivity of 62%and seems to be having a moderate value as screening test for nasal allergy.