Search

Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease characterized by a broad spectrum of clinical presentations and pathologic findings. CD44, a family of type I transmembrane glycoproteins involved in cell-cell and cell-matrix interactions, may orchestrate partially the cascade of inflammation, accumulation of myofibroblasts, and fibrosis leading to end-stage renal disease. To clarify the possible role of CD44 in the progression of IgA nephropathy, the expression of CD44 in glomeruli and the tubulointerstitial compartment was analyzed in 25 renal biopsy specimens of patients with IgA nephropathy and was correlated to histopathologic, serologic, and urinary parameters. The expression of CD44 correlated significantly with the degree of glomerular and interstitial damage, even better than the accumulation of α-smooth muscle actin-positive myofibroblasts, which is recognized as a reliable marker for the progression of IgA nephropathy. A positive correlation also was found between proteinuria and the expression of CD44 in the tubulointerstitial compartment. The glomerular and tubulointerstitial expression of CD44 correlated with the degree of renal damage in IgA nephropathy and could be a reliable marker of the progression of IgA nephropathy. CD44 may have a pivotal role in the cascade of renal inflammation and fibrosis. © 2002 by the National Kidney Foundation, Inc.

In earlier studies of sporadic amyotrophic lateral sclerosis (ALS), a disease of unknown etiology, the amount of metallothioneins (MTs), a group of small (6–7 kDa) metal-binding proteins, appeared higher in liver, kidney and spinal cord from patients than from non-neurologic controls. Immunohistochemically, the expression of MT in the central nervous system appeared limited to glia. Since the highly conserved MTs isotypes share antigenic epitopes, they could not be distinguished by immunological methods. It thus proved necessary to estimate the expression of each individual MT messenger ribonucleic acid (mRNA) by performing reverse transcriptase polymerase chain reaction (RT-PCR)-mediated analysis of tissue samples. Tissues selected included liver, motor cortex and cervical cord at C6; MT mRNAs analyzed included MT1A, 1B, 1E, 1F, 1G, 2A, and 3. Also, special care was taken to avoid interference by amplification of the 6 MT pseudogenes. Except of MT3, already known as brain-specific, and MT1B which was not expressed in any tissue, mRNA levels of the other MT genes tended to be higher in ALS than in control liver samples, but the differences did not attain statistical significance. In the nervous system, the diverse MT genes were expressed over a greater range in ALS than in controls, but exhibited no change in a consistent direction. At the motor cortex, changes seemed to be less pronounced than at C6. MT3 was expressed in the motor cortex and the cord. The results provide no evidence for either the induction of a specific MT repertoire, or for the inability of glia to express any MT gene in ALS. Because the semi-quantitative RT-PCR technique does not permit detailed comparisons between the subtypes of MT expressed in the various tissues, the question whether a single inductor may be held responsible for the elevation of MT in the ALS liver and nervous system remains open. In conclusion, ALS tissue remains capable of expressing all the major MT genes. MT, present in protoplasmic glia, arises locally and is not secondary to increases of hepatic or renal MT. Because MT3 is also expressed by the normal and ALS spinal cord, it is a central nervous system-specific and not only a brain-specific protein. Thus, the excess of MT in ALS liver seems to be an effect of slower catabolism rather than faster synthesis of protein.