Malignant disease of the lymphoid system in immunological perspective

The study of the structure of the lymphoid system has been an essential element in the overall progress of immunobiology. Study of the normal immune system, and especially study of immune deficiency disease, has revealed a remarkable degree of complexity within the lymphoid system, particularly at the cellular level. This complexity precludes the precise or definitive characterization of lymphoproliferative malignant disease by morphological criteria alone. However, new methodologies now available can be used to identify distinct lymphocyte subpopulations, each population possessing a characteristic set of markers or functions. As a result of these recent advances, the definition of lymphoproliferative malignant disease in immunological terms is entering a highly productive period.     

Severe dental aberrations in familial steroid dehydrogenase deficiency: a new association

Severe numerical dental aberrations are rare, and are most often seen as a part of certain syndromes. We here report on a Saudi Arabian family where first-cousin marriages have caused numerical and structural dental abnormalities linked to autosomal recessively inherited liver diseases. The two latest affected children in this family have had their liver defect successfully treated with fat-soluble vitamins and chenodeoxycholic acid, enabling us to study their dental development. One boy exhibits 11 supernumerary teeth, a general hypomineralisation and enamel hypoplasia, while an affected cousin successfully diagnosed at an early age, so far, only suffers from structural enamel defects. The children are otherwise healthy. There is no resemblance to any known syndromes. We suggest that the supernumerary teeth and the liver disease are caused by the same genetic defect, and represent a new association. The hypomineralisation, however, is most likely to result from vitamin deficiency secondary to malabsorption during the first years of life, before successful treatment was instituted.     

Inherited complement deficiency states: implications for immunity and immunological disease

The study of complement deficiency states and their influence on immune function has generated new insights and still provides a challenge to continued investigation. The association of classical pathway deficiencies (C1, C4, C2 or C3) with immunological diseases such as SLE and glomerulonephritis has contributed to current knowledge concerning complement-dependent immune complex handling and elimination. Susceptibility to systemic infection with encapsulated bacteria is encountered in most forms of inherited complement deficiency. Recurrent neisserial infection is the only clinical manifestation clearly associated with defects of the membranolytic sequence C5-C9, while deficiency of properdin, a component of the alternative activation pathway, appears to predispose to nonrecurrent meningococcal disease. Inherited complement deficiency is rare, but the perspective is widened by the more common occurence of acquired defects in immunological diseases, and the apparent requirement for efficient complement recruitment in host defense. Another aspect is the possibility that complement deficiency might alleviate or prevent inflammatory symptoms. Notably, complement deficiency has not been reported in classical rheumatoid arthritis. Considerations of this kind would be refuted or modified by findings of complement deficiency in single patients.     

Trigonocephaly: a new familial syndrome

Trigonocephaly was found in six relatives through three generations of one family. The propositus was ascertained at birth because of omphalocele. In addition to trigonocephaly, he had minor ear, vertebral, and genital abnormalities. His father had mild microcephaly, and both had minor eye abnormalities. None of the other four affected individuals had any other malformations. In this family, trigonocephaly is an autosomal dominant trait. The ratio of affected males to affected females was 5 to 1, and although the paucity of affected females is not statistically significant, we speculate that it may reflect variable expressivity or sex limitation of the trait. We conclude that the condition in this family represents a unique syndrome in which trigonocephaly is not associated with functional brain abnormalities and where craniosynostosis is limited to the metopic region.     

β-galactosidase deficiency: Prolonged survival in three patients following early central nervous system deterioration

Three adult patients from two families have shown slowly progressive neurologic deterioration since the age of 3 years, associated with profound beta-galactosidase deficiency. Although affected individuals from the two different families differ in degree of intellectual deficit, facial coarseness and spondyloepiphyseal dysplasia, all lack visceromegaly and macular red spots. The diversity of phenotypic expression in these patients and others previously reported suggests the existence of composite genotypes (compound and double heterozygosity).     

Hodgkin's disease: a tumor with disturbed immunological pathways

Hodgkin's disease is a lympltoid neoplasia characterized by low frequeny of malignant Hodgkin and Reed-Sternberg (H-RS) cells in an abundant background of non-neoplastic cells. H-RS cells and their neighbors interact via a complex network of cellular activation/adhesion molecules and cytokines. Here, Hans-Jürgen Gruss and colleagues suggest that H-RS cells can be regarded as antigen-presenting cells able to interact with surrounding T cells, resulting in an intense, bid ineffective, immune response.     

Celiac disease: an immunological jigsaw

Celiac disease (CD) is a chronic enteropathy induced by dietary gluten in genetically predisposed people. The keystone of CD pathogenesis is an adaptive immune response orchestrated by the interplay between gluten and MHC class II HLA-DQ2 and DQ8 molecules. Yet, other factors that impair immunoregulatory mechanisms and/or activate the large population of intestinal intraepithelial lymphocytes (IEL) are indispensable for driving tissue damage. Herein, we summarize our current understanding of the mechanisms and consequences of the undesirable immune response initiated by gluten peptides. We show that CD is a model disease to decipher the role of MHC class II molecules in human immunopathology, to analyze the mechanisms that link tolerance to food proteins and autoimmunity, and to investigate how chronic activation of IEL can lead to T?cell lymphomagenesis.     

Systemic lupus erythematosus: a combined deficiency disease

To date, the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. By critically analyzing clinical facts and laboratory data, a hypothesis is proposed: drug-induced lupus erythematosus (DILE) is linked to a deficiency in Coenzyme A (CoA) that is secondary to a deficiency in pantothenic acid. This hypothesis is used to explain the high incidence of SLE in females, the role of sex hormones in this disease and the mechanism underlying a flare. The actions of anti-malarials and steroids are also discussed. The protean clinical presentation of SLE is attributed to co-existing deficiencies of dietary factors in addition to pantothenic acid. Contributing factors to these deficiencies may include increased nutritional requirements resulting from gene mutations. Treatment is replacement therapy with doses of pantothenic acid that is hundreds of times higher than that of the Dietary Reference Intake (DRI) and other vitamins. Using this method, 12 SLE females were studied with promising results.