ANTI-IgG ANTIBODIES IN JUVENILE RHEUMATOID ARTHRITIS

ABSTRACT. Egeskjold, E.-M., Permin, H., Hørbov, S. and Graudal, H. (Rheumatism Research Unit of Aarhus University, Aarhus, Denmark). Anti-IgG antibodies in juvenile rheumatoid arthritis. Acta Paediatr Scand, 70:711,.–Sixty-two patients, 48 children and 14 adults, with juvenile rheumatoid arthritis (JRA) and 62 age and sex matched controls were studied for anti-IgG antibodies of the classes IgG, IgM and IgA by an indirect immunofluorescence method. 88 % of 48 children =≤16 years and in 64 % of 14 patients >16 years with JRA against 2 % of the controls. IgM anti-IgG occurred inIgG anti-IgG occurred in 4 % of the children, in 24 % of the adults and in 2 % of the controls. IgA anti-IgG occurred in 2 % of the patients and in none of the controls. The prevalence of IgG anti-IgG was the same in pauciarticular, polyarticular and systemic cases, whereas the titres were higher in polyarticular than in pauciarticular cases, and higher in children with a disease duration of more than 5 years. Higher titres were related to higher ESR and lower hemoglobin values. The relationship of higher titres to clinically active disease was not statistically significant. No relationship was found to age, sex, age at onset, or to the dureation of disease. The titres were not related to the concentrations of serum IgG or to the titres of antinuclear antibodies. IgG anti-IgG are common to all the clinical types of JRA, whereas antinuclear antibodies separate the systemic type from pauci- and polyarthritis. Their possible pathogenic significance must therefore be different.     

ANTINUCLEAR ANTIBODIES IN JUVENILE CHRONIC ARTHRITIS

ABSTRACT. One hundred patients with juvenile chronic arthritis (JCA) were studied with respect to granulocyte-specific and organ-nonspecific antinuclear antibodies (GS- and ON-ANA) in relation to clinical features of disease. Seventy-two were girls and 28 boys. Sixty-seven patients had IgG ANA, 31 IgM, 10 IgA, 6 IgD, 19 IgE and 35 had ANA, which fixed complement C3. Sixteen of 17 sera containing IgG GS-ANA were from girls. The prevalence of IgG GS-ANA increased with the number of joints affected. No patient with the acute febrile type of the disease had IgG GS-ANA or C3 fixing ANA. The prevalence of IgG ON-ANA did not differ significantly in the mono-, pauci-, polyarticular and acute febrile types of JCA. Patients showing clinical activity more frequently had IgG and IgM ANA and C3 fixing ANA. The high titers of ANA were most often seen in girls. Chronic uveitis occurred in 10 of the patients and IgG ANA were present in sera from all of these.     

HYPOHISTIDINEMIA IN JUVENILE RHEUMATOID ARTHRITIS

ABSTRACT. The mean level of plasma histidine in 86 children with rheumatoid arthritis was found to be significantly lower in comparison with that of controls. The possible influence of various drugs on the plasma histidine concentration is discussed.     

CARDIAC INVOLVEMENT IN JUVENILE RHEUMATOID ARTHRITIS

ABSTRACT. Cardiac involvement was diagnosed in 15 of 320 cases of JRA (4.7%) and was most frequent in children with active systemic disease. Ten children had pericarditis, 2 had myocarditis, 2 had peri-myocarditis and 1 had aortic valvulitis. The highest risk of heart involvement was found during the first three years but it could occur at any time. Recurrent episodes were seen in 60% of cases. The prognosis in pericarditis seems to be good since no patient developed cardiac tamponade or constrictive pericarditis and cardiac function evaluated by echocardiography was normal in all patients at follow-up. In patients with myocarditis and peri-myocarditis, a dilated left ventricle was found in 2 of 4 patients and 1 patient who died, had severe cardiac changes at autopsy. The prognosis in myocarditis thus seems to be worse. In valvulitis the prognosis depends on which valve is involved. The benefit of early treatment with corticosteroids is discussed.     

DOSAGE OF SALICYLATES FOR CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS A Prospective Clinical Trial with Three Different Preparations of Acetylsalicylic Acid

Abstract. 41 children with juvenile rheumatoid arthritis (JRA) and 6 with postinfectious arthropathies, aged 3–15 years, were treated with acetylsalicylic acid for 14 days during which time the patients were hospitalized. Three different acetylsalicylic acid preparations were used: a microencapsulated form, an enteric-coated form and standard acetylsalicylic acid tablets. Serum salicylate concentrations were measured by Trinder's photometric method. With doses of 90–120 mg/kg/day symptoms of salicylism appeared in about 50% of the cases. Daily doses of 2 g/m² (not exceeding 70 mg/kg) proved relatively safe in this study, whereas symptoms and signs of intoxication appeared at doses exceeding 3 g/m²/day. In this respect there were no significant differences between the three acetylsalicylic acid preparations used. The results of this study also suggest that the serum salicylate concentrations should not exceed 2000 μmol/1 (about 27 mg/100 ml). The symptoms of salicylism correlated closely with serum salicylate levels, which, in turn, correlated well with the dosage in g/m². Elevation of serum aspartate aminotransferase was noted in 1/3 of the cases. All of these had a dose exceeding 2 g/m², and the frequency of elevated enzyme activities increased with increasing dosage. In the group receiving enteric-coated form of acetylsalicylic acid, there were fewer positive benzidine tests (12%) than in the two other groups (22–28%).     

TRANSIENT REMISSION OF JUVENILE RHEUMATOID ARTHRITIS AFTER MEASLES

ABSTRACT. Yoshioka, K., Miyata, H. and Maki, S. (Department of Paediatrics, Kinki University School of Medicine, Osaka, Japan). Transient remission of juvenile rheumatoid arthritis after measles. Acta Paediatr Scand, 70:419, 1980.–A 4-year-old Japanese girl with systemic juvenile rheumatoid arthritis had an attack of measles. On the day following the first signs of measles she became afebrile and free of joint pain even though aspirin therapy was discontinued. The remission lasted for 10 days. It appears that the measles virus infection may have been responsible for the brief remission in this patient. The observation of a remission of juvenile rheumatoid arthritis after measles is extremely rare.     

BONE MARROW FINDINGS IN JUVENILE IDIOPATHIC ARTHRITIS

The diagnosis of juvenile idiopathic arthritis (JIA) is an exclusion one due to heterogeneous clinical presentation and lack of specific laboratory tests. The authors investigated bone marrow of 25 untreated children with JIA at the onset of the disease. Bone marrow smears were evaluated for cell populations as well as myelodysplastic features and compared to two control groups. The characteristic of bone marrow in JIA was myeloid hyperplasia and elevated plasmocyte count. There was no difference between JIA patients and control groups in terms of myelodysplastic features. These findings can be helpful in explaining hematological alterations in JIA.     

SARCOIDOSIS PRESENTING WITH MASSIVE SPLENOMEGALY IN A CHILD WITH A HISTORY OF IRIDOCYCLITIS AND SENSORINEURAL DEAFNESS

Childhood sarcoidosis is a rare multisystemic disorder that can have variable clinical presentations. A triad of skin, eye, and joint involvement is common in children younger than 5 years; however, pulmonary disease is more common in older children, similar to adults. The authors report the case of a 10-year-old girl who presented solely with massive splenomegaly. Her history was significant for iridocyclitis and unilateral sensorineural deafness at 6 and 7 years of age, respectively. A gallium scan showed diffuse splenic uptake, and the pathology of the spleen was consistent with a noncaseating granuloma, with no evidence of malignancy. A work-up for infectious etiology was unremarkable. This case demonstrates that the challenge in diagnosing sarcoidosis in young children stems from its ability to present in several unique clinical scenarios. It also reinforces the importance of tissue evaluation and the exclusion of other differential diagnoses, such as lymphoma, to confirm the diagnosis of sarcoidosis.     

NATURAL HISTORY OF JUVENILE RHEUMATOID ARTHRITIS A Follow-up Study of a Case with Special Reference to Clinical, Electroencephalographic and Neuropathological Findings

ABSTRACT. A detailed comparison between the clinical and EEG findings is made in a case of a boy with juvenile rheumatoid arthritis (JRA) who died at 15 years, 6.5 years after the beginning of the follow-up period. In the course of the disease, seven EEG recordings were made, showing a progressive diffuse slowing and disorganization with some improvement during short remissions. In relapses, diffuse slowing was associated with grave asymmetries in the EEG which, however, fluctuated and later disappeared without accompanying clinical or neuroradiological abnormalities. An abundancy of different residual findings, however, remained in the EEG after relapses. There were spike-and-wave paroxysms in every record except at the terminal stage. A stepwise slowing and disorganization was also seen in these paroxysms as background activity. The final cause of death was an intraventricular haemorrhage. No cerebral amyloidosis was found at autopsy. In conclusion, it is suggested that JRA is also a brain disease manifested as a cerebral vasculitis.     

IMMUNE COMPLEX MEDIATED TISSUE DAMAGE IN THE LUNGS OF CYSTIC FIBROSIS PATIENTS WITH CHRONIC PSEUDOMONAS AERUGINOSA INFECTION

Høiby, N. and Schiøtz, P.O. (Statens Seruminstitut Department of Clinical Microbiology, Rigshospitalet and the Paediatric Department TG, Rigshospitalet, Copenhagen, Denmark). Immune complex mediated tissue damage in the lungs of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand; suppl 301: 63-73. — Evidence has accumulated which supports the following mechanism of tissue damage in the lungs of cystic fibrosis (CF) patients during chronic P. aeruginosa lung infection:
In CF chronic P. aeruginosa infection with mucoid strains is characterized by persistent presence of P. aeruginosa antigens in the lungs and simultaneous presence of many precipitating antibodies against these antigens in serum and sputum.
Formation of immune complexes in the lungs between these antigens and antibodies are indicated by the detection of immune complex activity in serum and especially in sputum. Immune complex-mediated activation of complement components in the lungs of such CF patients has been demonstrated. The activation of complement leads to formation of C3a and C5a split products, which lead to liberation of histamine from basophil leukocytes, i.e. inflammation which is also reflected in elevated acute phase proteins in serum. Evidence of this process has also been found as a type I skin test when P. aeruginosa antigens are injected intracutaneously in these patients. Liberation of serotonin from thrombocytes mediated by P. aeruginosa antigens in the presence of antibodies from these CF patients, causing inflammation, has been shown. Attraction of neutrophils to the lungs mediated by immune complex activated complement split products, ingestion of the immune complexes by the neutrophils, and liberation of proteolytic enzymes from the neutrophils, i.e. tissue damage, has been demonstrated, and goes on because immune elimination of the bacteria is not accomplished. The therapeutic consequences are discussed.     

INSULIN ANTIBODIES IN THE SERUM OF DIABETIC CHILDREN TREATED FROM THE DIAGNOSIS OF THE DISEASE WITH HIGHLY PURIFIED INSULINS

Abstract. Fitly-one diabetic children, treated with highly purified, porcine insulins from the diagnosis of the disease were studied for the development of insulin antibodies during the first years of treatment. Sera were obtained before the start of treatment and at repeated intervals thereafter. Serum insulin antibodies were measured by three methods in three laboratories. Twenty-nine children were treated with R.I. (rare immunogenic) insulins at one department and 22 with MC (monocomponent) insulins at the other department. Before the start of treatment, serum insulin antibodies were almost invariably zero or below the limit of detection. During the first year a considerable number of cases, more than that reported for adults, formed detectable amounts of antibodies, and more so in the R.I. than in the MC series. The levels were however definitely lower than those observed with the Same methods in diabetic children on conventional insulins. Analysis of variance showed no differences between the various age groups. No significant correlation was found between the highest titre of serum insulin antibodies on the one hand and insulin dose or glucosuria on the other hand. The results confirm the concept that children form antibodies to insulin more actively than adults.     

CHRONIC AUTOIMMUNE HEMOLYTIC ANEMIA IN CHILDHOOD WITH COLD ANTIBODIES, APLASTIC CRISES, AND FAMILIAL OCCURRENCE

A report is given of two sisters who developed chronic autoimmune hemolytic anemia in their fourth and twelfth years of age, respectively. The serological findings were different in the two cases. In patient 1, a typical cold agglutinin with a titer of 256 at 4^oC was found in the serum, and only complement on the red cells by the direct Coombs' test. The serum hemolysed trypsinized red cells at 37^oC. Her sister had warm type hemolytic anemia with a γG antibody on her red cells. In case 1, the clinical course has been severe, with several exacerbations of the hemolytic process accompanied by erythroid aplasia in the bone marrow. Whereas acute autoimmune hemolytic anemia with cold antibodies is not rare in children, and may be elicited by mycoplasma or viral infections, chronic autoimmune hemolytic anemia is rarely seen before adulthood. The typical, chronic cold hemagglutinin disease with hemoglobinuria and Raynaud's phenomena has not been described in childhood, and was not present in our case. It is suggested that the disease in the case presented may have started as the result of an acute infection, and that for one reason or another (genetic predisposition?) the process has not shown the usual self-limited course. Although a familial–probably genetic– predisposition exists for several autoimmune diseases, familial occurrence of autoimmune hemolytic anemia has rarely been observed. The authors have found nine convincing reports in the literature, and in only one of the reported families did the hemolytic anemia develop in childhood. In families predisposed to autoimmune diseases, a variety of γ-globulin disturbances and autoimmune disorders are often found. The presence of a more fundamental, genetic aberration of the immune apparatus, preventing a normal immune homeostasis, may therefore be postulated. A brief comment is made on the possible mechanism of the repeated periods of erythroid aplasia in the patient with cold antibodies. It is suggested that a second antibody, causing hemolysis of trypsinized red cells at 37^oC may be of importance by damaging the red cell precursors. The presence of this antibody may also possibly explain why the severity of the clinical picture of the patient did not seem to be related to exposure to cold.     

IMMUNE RESPONSES IN PATIENTS WITH OBSTRUCTIVE JAUNDICE OF INFANCY

ABSTRACT. To investigate possible involvement of immune responses in the pathogenesis of obstructive jaundice in infancy we measured antibody to liver specific lipoprotein (LSP) by radio immunoassay and immune complexes by their ability to bind Clq in sera from 16 patients with extrahepatic biliary atresia and 16 with neonatal hepatitis and 13 age matched controls. Anti-LSP was present in 6 of 16 with preoperative biliary atresia and 6 of 16 with hepatitis. Mean percentage Clq bound was higher in hepatitis (22 SD 15 %) than preoperative biliary atresia (11.1 SD 2.3 %). Nine of 16 hepatitis patients had elevated Clq binding as compared with 1 of 16 with biliary atresia. The highest value for anti-LSP and Clq binding were found in sera from patients with histologically severe hepatitis and hepotitis associated with specific viral or bacterial causes. Anti-LSP was significantly raised 5 months post-operatively in all of 6 patients with biliary atresia and poor biliary drainage but only 2 of 5 survivors. Elevated Clq binding was detected in 6 of 7 with poor drainage and 1 of 7 survivors at the same stage. Anti-LSP and Clq binding fell in 4 patients with neonatal hepatitis on recovery. These findings suggest that immunological mechanisms, possibly involving antibody to hepatocyte membrane components and immune complexes, may be involved in the pathogenesis of progressive liver disease in biliary atresia.     

OCCURRENCE OF OLIGOCLONAL GAMMAGLOBULIN IN THE CSF OF CHILDREN WITH PROLONGED and CHRONIC CNS-INFECTIONS

Abstract. Siemes, H., Siegert, M. and Hanefeld, F. (Department of Paediatrics, Free University of Berlin, F.R.G.). Occurrence of oligoclonal gammaglobulin in the CSF of children with prolonged and chronic CNS-infections. Acta Paediatr Scand, 70: 91, 1981.–CSF-proteins of 1770 children and adolescents with different neurological diseases and of 75 controls were examined by zone electrophoresis in agarose gel electrophoresis and by immuno-fixation electrophoresis. The quantitative evaluation of the phoretograms by an analog computer revealed oligoclonal changes of the gamma-globulin profile in 53 patients with subacute or chronic CNS-infections and in 5 children with a medulloblastoma. Seventeen of 37 children with congenital infections had 1–5 oligoclonal gamma-fractions consisting of IgG. Five to seven oligoclonal IgG fractions were detected in each of 16 children with SSPE. All 6 adolescents with multiple sclerosis had 2–5 oligoclonal IgG fractions. One to five oligoclonal gamma-bands occurred transiently in the CSF of 4 children with prolonged meningoencephalitis caused by different viruses, in 3 children with a prolonged non-bacterial meningitis of probable viral origin, in 2 infants with prolonged bacterial meningitis after corticosteroid therapy, and in 1 child with prolonged bacterial meningitis during cytostatic therapy. Four to six oligoclonal gamma-subfractions were found at different times during progressive viral encephalitis that developed during maintenance therapy of acute lymphoblastic leukaemia, and in 2 patients with chronic meningoencephalitis of unknown origin. Since oligoclonal gamma-globulin was detected almost invariably in the CSF of patients with prolonged or chronic neurologic infections, this finding implies persistence of antigens in the CNS and pathologic invasion of lymphocytes with selective proliferation of antigen-stimulated clones.     

INFLUENCE OF MATERNAL GUT FLORA AND COLOSTRAL AND CORD SERUM ANTIBODIES ON PRESENCE OF ESCHERICHIA COLI IN FAECES OF THE NEWBORN INFANT

ABSTRACT. From 29 healthy newborn infants and their mothers faecal, serum and milk specimens were obtained on several occasions from one to nine weeks after delivery. Predominant faecal E. coli were serotyped with regard to the O antigen and milk and serum were analysed for their content of E. coli O antibodies by the enzyme-linked immunosorbent assay. In five cases the babies acquired the same O serotype as was found in the stools of their mothers but in 12 out of 29 cases infant and mother never had any dominating faecal E. coli O type in common. There was no apparent correlation between the patterns of feeding and interchange of bacteria. Klebsiella/Enterobacter was the dominating facultative organism on at least one occasion in half the infants. The newborns received coiostral IgA and transplacental circulating IgG antibodies against a great number of E. coli O serotypes. These antibodies did not prevent intestinal colonization, as judged from cultures of faeces.