Draft:Jean Berger (Pathologist)

Jean Berger

Jean Berger (1930–2011)

Not to be confused with Jean Berger the musician or Jean Berger the painter. Jean Berger is a French renal pathologist who first described IgA nephropathy. His exceptional work coincided with the flourishing of renal biopsy as a principal investigative tool in kidney disease. Berger died on 22 May 2011. As he admitted before death, the pathogenesis of IgA nephropathy remains mysterious despite all the great efforts.. For quite some time, IgA nephropathy was referred to as “Berger’s Disease” (not to be confused with Buerger’s Disease, or thromboangiitis obliterans), though it has largely been replaced by IgA Nephropathy in recent times.. The new technique of immunofluorescence microscopy, undertaken with fresh renal biopsy material to identify the presence of immunoglobulins and complement components, was still regarded as an experimental technique. Berger applied the technique to renal biopsies.

Early life

Little is known about his early and personal life. Berger was born in Paris on 17 September 1930.He became Interne des Hôpitaux de Paris (resident) in 1954. Later moved to the Department of Nephrology under supervision of Professor Jean Hamburger at the Necker-Enfants Malades Hospital in Paris where he showed early interest in pathology. In 1960, Berger was qualified as a specialist in medicine and wrote a thesis entitled, “Contribution of the renal biopsy to the pathological knowledge of the kidney diseases.”

Early Glomerulonephritis

Since the clinical description of “Bright’s disease” in 1827 by Richard Bright, discussed by many observers was non-stopped. Bright’s work was done just before the new microscopes were introduced into clinical practice, following which microscopy of renal tissue. Gottlieb Gluge’s and Gabriel Valentin’s studied renal histology extensively ten years later. The macroscopic and microscopic appearances of nephritic kidneys (“Bright’s disease”) became known. The major advance of Valentin in 1837 was the invention of a double- bladed knife, which allowed the cutting of “thin” sections of tissue for examination under the microscope. Stained microscopic material was introduced in the 1850s-1860s, and hence renal morphology dominated thinking. There was confusion between the description and clinical observation because different appearances could be seen in the kidney samples that remained beyond the First World War. That confusion remained until 1968 when Jean Berger and his colleagues differentiated aggregates visible on fluorescent microscopy by immunoglobulin class, IgA as opposed to IgG.

Renal Biopsy

Renal biopsy had initially emerged in the early 1950s and was used in the classification of glomerular diseases based on morphology defined by light microscopy. Electron microscopy was available in the late 1950s and first applied to kidney biopsy material. With Pierre Galle, Berger described “fibrinoid inter-capillary deposits” in patients with chronic glomerulonephritis using an electron microscopist. This was the first step toward his future description of IgA nephropathy. They also were the first to describe dense deposits within the glomerular basal membranes. Fluorescently labeled antibodies were first used to detect proteins in the early 1950s, but until the mid-1960s very few laboratories offered this technique. In the late 1950s, Berger had additional training in London with Deborah Doniach; the pathologist to implement the fluorescent techniques to the kidney biopsy. By 1963, antibodies were commercially available, but laboratories studying immunofluorescence in kidney biopsies mostly used only anti-IgG reagents, as IgG was thought to be the predominant immunoglobulin class involved in the immunopathogenesis of nephritis. In Necker- Enfants Malades Hospital, Berger in collaboration with Professor Bernard Antoine, an immunologist, developed the methodology for immunofluorescence. They tested commercial sera and labeled them with fluorescein; anti-IgA specificity was confirmed with an anti-IgA serum produced by Professor Maxime Seligmann. Later, immunofluorescence technique was performed in the laboratory of Dr. Halina Yaneva. Liliane Striker (née Morel-Maroger) has published a memoir from her own experience as a research fellow in the 1960s, in which she describes the excitement of those days when Berger identified the new nephropathy that was to bear his name.

IgA Nephropathy

At the time Jean Berger reported his observations he was working as a pathologist in Paris at Hôpital Necker, and was also Professor at the Université René Descartes. In 1967, Berger presented a variant of renal lesions based on their immunofluorescence pattern. Among these findings, he identified glomerular IgA deposits in a few patients with chronic glomerulonephritis. In the winter of 1968,at the Société de Néphrologie in Paris, his oral report was followed by the publication in French of a summary less than one page long. This report, now cited time and again all over the world, was entitled “Les dépôts intercapillaires d’IgA-IgG.” Later, Berger described a nephropathy characterized by the presence of mesangial IgA–IgG deposits in 55 patients with a range of light microscopy appearances, most commonly focal glomerulonephritis. He stated that 22 of them “had one or several bouts of gross hematuria which usually occurred during a sore throat.” He added, “The course of the disease appeared to be remarkably slow,” but in one patient renal transplantation was needed, and biopsy of the transplant showed recurrent IgA deposits. IgA deposits were also identified in lupus and Henoch–Schönlein purpura nephritis. Initially there was some reluctance to give credence to Berger’s observations by acknowledging IgA nephropathy as a distinct clinicopathological entity. Moreover, it was thought that the disease was confined to France, but the finding of predominant mesangial IgA in patients with mesangial or focal glomerulonephritis was soon realized to be common worldwide. This was the reason why different names have been used for IgA nephropathy over the past 40 years. In 1972 the term ‘Berger’s disease’ was first proposed for IgA nephropathy by a French group, although subsequently this term was sometimes restricted to those patients who had recurrent episodes of gross hematuria. Berger and his colleagues at the Necker-Enfants Malades Hospital went on to show that mesangial IgA deposits recurred frequently in transplanted kidneys, although they also mentioned: “the high incidence of recurrence was not a contraindication to transplantation.”.Berger further observations identified similar mesangial IgA deposits also in Henoch-Schönlein purpura. Berger was interested by the high frequency of IgA nephropathy worldwide, but he specifically reported that in France IgA nephropathy accounted for 20–25% of cases of primary glomerulonephritis and was an important cause of terminal renal disease, accounting at that time for 15% of cases of glomerulonephritis requiring renal transplantation. Berger’s later tried to understand the pathogenesis of the disease, his work concluded that circulating rather than local kidney abnormalities were responsible for the disease. Berger’s original reports in 1968–1969 were novel observations; they introduced a new level of descriptive classification into the study of glomerulonephritis. This report, cited many times allover the world, was entitled “Les dépôts intercapillaires d’IgA-IgG”. Dr Nicole Hinglais; the electron microscopist was his co-author at that time.. The presence of IgA deposits remains to date the only means to diagnose IgA nephropathy, now recognized to be the most common glomerulonephritis. Jean Berger was a hard worker and eager reader of kidney literature. One of his last sentences published stated that “Despite this effort, the pathogenesis of IgA nephropathy remains mysterious.