Cellular immune responses of patients with juvenile chronic arthritis to retinal antigens and their synthetic peptides.

The objective of this study was to determine the proliferative responses of peripheral blood lymphocytes of ocular antigens like retinal S-antigen, peptides M and G of S-antigen, yeast histone H3 peptide 106-121 homologous to peptide M and peptide R16 of interphotoreceptor retinoid binding protein (IRBP) in children with juvenile chronic arthritis (JCA). We have studied the in vitro proliferative response of peripheral blood lymphocytes from 41 patients with JCA (10 with and 31 without uveitis) and 23 healthy controls against the above antigens. The responders were retested after 1 or 6 months. Fifty (5/10) and 9.7% (3/31) of JCA patients with and without uveitis, respectively, responded (stimulation index > 3) to S-antigen or one of its peptide listed above or yeast histone H3 peptide or R16 of IRBP. None of the healthy controls responded to any of these antigens. The difference in the frequency of responders (SI > 3) between JCA associated with uveitis and healthy controls was statistically significant (p = 0.001). Similarly, the difference between JCA with and without uveitis was also significant (p = 0.013). Our findings suggest that these antigens may have a role in the pathogenesis of uveitis in a subset of patients with JCA.

Cellular immune response to retinal S-antigen & interphotoreceptor retinoid binding protein fragments in idiopathic human uveitis.

The role of retinal antigens in idiopathic human uveitis has been studied in 38 patients of uveitis, and 30 patients of systemic connective tissue disease (CTD) and 30 healthy volunteers. Lymphocyte proliferative responses were tested in vitro against native S-antigen, its uveitopathogenic peptides (peptide M, peptide G), yeast histone H3 peptide and uveitopathogenic fragment of interphotoreceptor retinoid binding protein (IRBP: R16) to establish their role in pathogenesis of human uveitis. Seven patients with uveitis, and none among CTD patients and healthy volunteers, responded (stimulation index > 3) to at least one retinal antigen used. One uveitis patient showed response to native S-antigen, peptide M and yeast histone H3. One responded to both S-antigen and peptide M and another responded to both peptide G and R16 peptide. Two responded to S-antigen only, one to peptide M and one to peptide G. In addition, one uveitis patient responded to yeast histone H3 only. These results suggest that retinal antigens may play a role in the etiopathogenesis of a subset of idiopathic human uveitis.

Immune response of infants to fractional doses of intradermally administered inactivated poliovirus vaccine.

Seventy eight infants aged 6-8 weeks received either two doses of 0.1 ml of inactivated poliovirus vaccine (IPV) intradermally 8 weeks apart (group A) or three doses 4 weeks apart (group B). Pre- and 4 weeks post-immunization serum samples were tested for the presence and titer of neutralizing antibody to poliovirus types 1, 2 and 3. The seroconversion rates to poliovirus types 1, 2 and 3 were 90, 70 and 97%, respectively, among infants in group A and 90, 80 and 98%, respectively, in group B; in children without pre-existing maternal antibody, seroconversion rates were 100% to all three poliovirus serotypes in both groups. These rates were comparable to those in children receiving five doses of OPV or two doses of intramuscular IPV. Intradermal administration of fractional doses of IPV may be a less expensive alternative for use in developing countries.

Experimental poliomyelitis in bonnet monkey. Clinical features, virology and pathology.

We have investigated the distribution of virus and the pathology in the spinal cords of bonnet monkeys (Macaca radiata) with experimental paralytic poliomyelitis induced by inoculating poliovirus type 1 (Mahoney) into the right ulnar nerve. Viraemia and alimentary tract infection due to the inoculated virus were found in all monkeys. Between two and seven days after the onset of limb paralysis, the animals were killed and the spinal cord examined. Virus was isolated from the cervical enlargement, thoracic region and lumbar enlargement in titres ranging from 10(2.5) to 10(6.4) TCID50/gram of tissue. Cellular infiltrate, perivascular cuffing, early and late neuronal damage such as chromatolysis, nuclear pyknosis, retraction of the cytoplasm and neuronophagia were seen distributed throughout the spinal cord. This experimental animal model resembles human paralytic poliomyelitis clinically and pathologically.

Ulnar nerve inoculation of poliovirus in bonnet monkey: a new primate model to investigate neurovirulence.

A new monkey model of poliovirus neurovirulence has been developed avoiding the currently used intraspinal injection route which traumatizes the spinal cord. Poliovirus type 1 (0.1 ml) was inoculated into the ulnar nerve of bonnet monkeys (Macaca radiata) at the right elbow. Five monkeys were inoculated with 10(7) TCID of LSc/2ab (Sabin vaccine strain); none developed any illness. Limb paralysis, clinically resembling spinal poliomyelitis in children, developed in all four monkeys given greater than or equal to 10(5) TCID50 of Mahoney strain, and in three of four monkeys given 10(4) or 10(3) TCID50. Higher functions and cranial nerves were not affected. Paralysis occurred more frequently in the lower limbs (11 limbs in seven monkeys) than in upper limbs (six limbs in seven monkeys). The incubation period, from inoculation to onset of paralysis, ranged from 5 to 12 days. Further progression of paralysis to other limbs occurred within 2 to 6 days. No illness developed in two monkeys given 10(2) TCID50 of Mahoney virus. All monkeys given LSc/2ab and those given greater than 10(2) TCID50 Mahoney virus developed humoral antibody response; however, infection of the gastrointestinal tract was detected by virus isolation from throat swabs and stools only in monkeys given Mahoney virus, but not in those given LSc/2ab. Thus, intraneural spread of Mahoney virus to the spinal cord, neurovirulence of Mahoney but not of LSc/2ab and retrograde gastrointestinal infection with Mahoney but not with LSc/2ab are the features of this experimental model.

Cellular immune response to retinal S-antigen and interphotoreceptor retinoid-binding protein fragments in Eales' disease patients.

The role of retinal antigens in Eales' disease was studied in 24 patients and an equal number of healthy controls. Lymphocyte proliferative responses were tested in vitro against native S-antigen, its uveitopathogenic peptides (peptide M and peptide G), yeast histone H3 peptide and uveitopathogenic fragment of interphotoreceptor retinoid-binding protein (IRBP; R16) to establish their role in the pathogenesis of Eales' disease. Out of 24 Eales' disease patients, 6 showed significant proliferative response against S-antigen, its uveitogenic fragments or IRBP. None among the controls showed any response to any retinal antigen used in this study. There was no statistically significant difference in the response to purified protein derivative between patients and controls. These results suggest that retinal antigens may play a role in the etiopathogenesis of Eales' disease. An extraneous agent that could result in exposure of normally sequestered uveitopathogenic antigens of the immune system, leading to an exuberant immune response in the eye may initiate the disease.