HISTORY

 

Jean Berger, the man who identified IgA Nephropathy by J. Feehally

Although IgA nephropathy is the name most commonly used for the renal disease we study, many other terms have been used for it over the last 30 years. Most have derived from a description of the features of the disease found on renal biopsy: for example mesangial IgA disease, IgA glomerulonephritis, and IgA-IgG nephropathy.
But one title often used in the past for IgA nephropathy stands out: Berger’s Disease, named after Jean Berger, the French pathologist who published the first description of IgA nephropathy as we recognise it today.

Jean Berger in the 1960’s

 

At the time Jean Berger made and reported his seminal observations he was working as a pathologist in Paris at Hôpital Necker, and was also Professor at the Université René Descartes . In the late 1960’s renal biopsy was an increasingly used technique for investigating renal disease and the nephrologists with whom Berger worked at Hôpital Necker and Hôpital Tenon in Paris were among the leaders in this new wave of work. A classification of glomerulonephritis had been developed based on the various pathological appearances seen on specimens taken by renal biopsy, but in the mid-1960’s it was largely based on the morphology as seen on light microscopy. 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 and recognised that there was a group of patients, not properly defined before, in whom the dominant finding was the deposition of IgA in the glomerular mesangium. Electron microscopy showed there were mesangial electron dense deposits corresponding to the mesangial IgA. Light microscopy showed mesangial hypercellularity, which was usually focal and segmental. Interpreting his findings in the light of clinical information, he realised that typically these were young adults with low grade proteinuria and microscopic haematuria, and most often with recurrent episodes of macroscopic haematuria coinciding with upper respiratory tract infection.
The first public appearance of his findings was modest: an oral report to the French Société de Néphrologie in the winter of 1968, followed by the publication in French of a summary less than one page long (1). This report, now cited time and again all over the world, was entitled “Les dépôts intercapillaires d’IgA-IgG”. His co-author was an electron microscopist, Dr Nicole Hinglais.

At first the importance of Berger’s findings was poorly appreciated in many circles. A number of influential authorities doubted whether IgA nephropathy should be accorded the right to be identified as a distinct pattern of glomerulonephritis. Many of these patients, before Berger’s description of the immunofluorescence findings of IgA, would have been classified as having ‘focal nephritis’, a term in wide use at that time which some were reluctant to discard. [For a description of the development of the term focal nephritis, please go to the adjacent article by Professor Stewart Cameron]. Rapidly other renal pathologists identified similar cohorts of patients, and it became clear that IgA deposition was indeed the commonest finding in patients with diffuse and focal mesangial proliferative glomerulonephritis; IgA nephropathy had been defined.
Berger followed his original descriptive phrase, dépôts intercapillaires d’IgA-IgG (1), by using the term ‘nephropathy with mesangial IgA-IgG deposits’ (2). But this was soon replaced by a number of other terms, including IgA nephropathy, mesangial IgA disease, mesangial IgA glomerulonephritis, IgA-IgG nephropathy of which IgA nephropathy has proved the most enduring. In the early years the condition was often called Berger’s disease, although this term was sometimes restricted particularly to those patients who had recurrent episodes of macroscopic haematuria.
Within a short time, Berger made further seminal observations. Firstly, he identified that similar mesangial IgA deposits also typified the glomerulonephritis associated with Henoch-Schönlein purpura (2), which indeed was morphologically often indistinguishable from IgA nephropathy. Secondly, he showed that recurrence of mesangial IgA deposits occurred frequently in kidneys transplanted into patients who had developed end-stage renal disease due to IgA nephropathy (3). Thirdly, Berger also published a major description of the secondary form of IgA nephropathy associated with alcoholic liver disease (4).
With these observations, Berger established a new understanding of these common groups of patients with glomerulonephritis, and it soon became clear that IgA nephropathy was the commonest pattern of glomerulonephritis found wherever renal biopsy was widely practiced. The glomerular disease in these patients could now be identified and classified, and studies of their pathogenesis, clinical course and treatment could begin to be established.

Since Berger’s observations were so innovative and influential, why has the term ‘Berger’s disease’ gradually fallen out of use? Perhaps because eponymous titles for diseases are becoming less fashionable. But much more importantly, it seems that Berger himself did not wish the term to persist. This naturally modest man preferred not to see his name attached to the disease he first described.
I myself only met Berger once – at an International Symposium on IgA Nephropathy held under the auspices of the IgA Club [the forerunner of the International IgA Nephropathy Network] in Bari, Italy in 1987. In retrospect I recall the occasion vividly, but at the time I had no idea of the identity of the charming and modest man with whom I had breakfast; and I suspect it is typical of him that only later did I realise from others his true identity.

Jean Berger in the 1980s

 

Berger was also much more than a researcher. Dr Liliane Striker has published a delightful memoir of Berger, from her own experience as a young research fellow in Berger’s laboratory in Hôpital Necker in the 1960’s, in which she describes the excitement of those early days when Berger identified IgA nephropathy. But also she tells vividly of Berger’s great skills not only as a researcher, but as a teacher and diagnostician (5).

Dr Berger himself lives quietly in retirement in Paris. He does not wish to revisit the past. We respect his privacy and wish him well. But we also acknowledge his seminal descriptions which laid the way for every piece of clinical observation, treatment investigation, and laboratory research on IgA nephropathy which have followed in the 35 years since his famous first report.

John Feehally
Leicester General Hospital, UK
January 2003

References

1. Berger J, Hinglais N. Les dépôts intercapillaires d'IgA-IgG. J Urol Nephrol 1968; 74: 694-5
2. Berger J. IgA glomerular deposits in renal disease. Transplant Proc 1969; 1:939
3. Berger J, Yaneva H, Nabarra B, Barbanel C. Recurrence of mesangial deposition of IgA after renal transplantation. Kidney International 1975; 7:232-41
4. Berger J, Yaneva H, Nabarra B. Glomerular changes in patients with cirrhosis of the liver. Adv Nephrol 1978; 7:1-4
5. Striker L. Les depots intercapillaires d'IgA-IgG. J Amer Soc Nephrol 2000; 11(10):1957-59