Thursday, August 17, 2017

History of IIgANN

HISTORY of the International IgA Nephropathy Network

The IgA Nephropathy Club, 1987-2000

During the Second International IgA Nephropathy Symposium in Bari, Italy in 1987, some of the  participants, Giuseppe D'Amico from Italy, Hideto Sakai from Japan, Tony Clarkson from Australia and Bruce Julian from the United States, met to organize an informal group, the IgA Nephropathy Club. The purpose was to increase awareness of the clinical importance of the disease and to encourage national and international collaboration in clinical and basic science research.

Some of the initial approaches were to better define the clinical features in adults and children, and to search for clinical and laboratory markers to predict the long-term prognosis. Everyone agreed that the two symposia, the first having been held in Milano, Italy in 1983, had been well organized and served to personalize relationships between investigators who had a common goal to solve the mysteries and puzzles presented by IgA nephropathy.

IgA nephropathy had become recognized as the most common form of primary glomerulonephritis in the short time span since its initial description by Drs. J Berger and N. Hinglais in 1968. However, up to that point, the clinical impact of the disease was underappreciated by nephrologists and general physicians in many countries. The gatherings at the symposia spawned productive collaborative clinical and laboratory undertakings. These efforts increased awareness of the disease in many medical communities and agencies funding medical research.

Over the ensuing years, a series of international symposia have been held every two to four years. The members of the IgA Nephropathy Club encouraged interested investigators to organize meetings at venues that have rotated between continents, whereby young scientists, physicians, and students in many regions of the world could more easily attend. Here are the symposia so far organised: 

Year

Venue

Organisers

1983 

Milano, Italy

G D’Amico, L Minetti, C Ponticelli

1987

Bari, Italy

FP Schena, SN Emancipator

1988

Washingon DC, USA

B Julian,  I Greifer

1990 

Tokyo, Japan

H Sakai, O Sakai, Y Nomoto

1992

Nancy, France

MC Bene, GC Faure, M Kessler

1994 

Adelaide, Australia

AR Clarkson, AJ Woodroffe

1996

Singapore

KT Woo, G Lee

1998

Leiden, Holland

LA van ES, M Daha

2001

Kuongju, Korea

M-J Kim

2004 

St. Etienne, France

F Berthoux

2006

Tokyo, Japan

Y Tomino

2009

Stresa, Italy

R Coppo, J Feehally

2013 

Nanjing, China

Z-H Liu

 

The scientific programmes for these symposia  has generally included overviews and summaries by senior clinicians and laboratory scientists, as well as free communications of novel data. The topics at these meetings have touched on most of the state-of–the-art work in the field. The interactions between the attendees were often instrumental in stimulating new investigative approaches. The opportunity to review the results and discuss the implications was frequently beneficial in the preparation of more polished manuscripts to be submitted for publication.

The International IgA Nephropathy Network (IIgANN), 2000-Present

In 2000 the IgA Nephropathy Club recognized the need to rejuvenate its format. A more encompassing name was selected, the International IgA Nephropathy Network (IIgANN). The new efforts included changing its approach to a management committee with additional members from more research centers.

The Steering Committee from 2000-2003 included: Rosanna Coppo [Torino], John Feehally [Leicester],  Bruce Julian [Birmingham], John Knight [Sydney], Renato Monteiro [Paris], Hideto Sakai [Isehara]

A website was established to better disseminate scientific information and educational materials to physicians, investigators, students and the general public.

The Steering Committee from 2003-2008 included:  Rosanna Coppo (Torino) Secretary-Treasurer,  John Feehally (Leicester) Chair, John Knight (Sydney), Bruce Julian (Birmingham) ,Renato Monteiro (Paris), Yasuhiko Tomino (Tokyo). 

About Our Logo

IIGANN IconThe logo is an artist’s impression of the polymeric IgA molecule showing J chain linking two monomer IgA molecules lying end to end with their Fc portions adjacent.

The logo was drawn by Jasper Knight, a well known young Australian artist. Jasper created  the logo at the request of his father, John Knight, paediatric nephrologist and member of the IIgANN Steering Committee in the first decade of this century.

 

History of IgAN

Contents

  1. Jean Berger – the man who identified IgA Nephropathy- John Feehally
  2. Berger’s disease before Berger -  J Stewart Cameron

To discover more, go to:

Feehally J, Cameron JS IgA nephropathy: progress before and since Berger. Am J Kidney Dis. 2011 Aug;58(2):310-9

Jean Berger – the man who identified IgA Nephropathy (By  John 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.

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 read 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? Chiefly perhaps because eponymous titles for diseases are becoming less fashionable. But we should not let future generations of nephrologists forget the seminal contribution made by Berger, even if his name no longer identifies the entity he discovered

Berger's Disease Before Berger
By J Stewart Cameron

When in 1968 Jean Berger and his colleagues in Paris described glomerular mesangial deposition of IgA in some nephritides, they did more than make a novel observation : they introduced a whole new level of descriptive classification into the study of clinical glomerulonephritis. This action illustrated only too well the morass of descriptions and classification of glomerular diseases had fallen into, which still awaits a full resolution. To understand what "Berger's disease" might mean and how it evolved, we have to look back a long way.

Classifications of nephritis 1820-1970
Since Richard Bright's universally-known book of 1827, and Gottlieb Gluge's and Gabriel Valentin's much less well-known pioneering studies of renal histology ten years later, the clinical manifestations and the macroscopic and microscopic appearances of nephritic kidneys ("Bright's disease") had been discussed by many observers. Bright's work was done just before the new improved apochromatic microscopes were introduced into clinical practice, following which microscopy of renal tissue – and urine – became a regular feature of clinical enquiry (although Bright made one microscopical study in 1839-42 with Joseph Toynbee). 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 (unstained) under the microscope.
Thus, ideas about nephritis were dominated from 1840 onwards by the combination of clinical observation and the macroscopic and microscopic observation of renal tissue obtained after the death of the patient. To begin with, tissues were unstained for microscopy; but the introduction of natural dyes (such as carmine) in the 1850s, and then synthetic stains from 1860 onwards meant that renal morphology dominated thinking. There had been an uneasy tension between this level of description and clinical observation from the start – very early it was noted that in one clinical setting (say dropsy and proteinuria) a number of different appearances could be seen in the kidney. These appearances were initially described in the 1840s and 1850s as either a fatty kidney with normal or nearly normal glomeruli, or in contrast a form in which the presence of cells and tubular destruction predominated. Debate about the relationship between these two forms, and their relationship to scarred granular kidneys, dominated renal pathology up to and beyond the First World War.

Pathologists naturally felt that their level of description was more fundamental than clinical classifications, and that the underlying "diseases" were expressed primarily in morphological terms. Thinking was - and remained - confused. Pathological terms (such as the notorious "nephrosis") slipped sideways and came to be used for clinical syndromes, and vice versa. A further, apparently even more fundamental, layer of description was introduced when the aetiology of some of the appearances was teased out: "post- streptococcal nephritis" was the first, in the 1880s as bacteriology was born and the streptococcus identified ( "scarlatinal nephritis" had existed since 1740 or earlier).

Then the idea of time came to influence classification: first with the crude description of "acute" and "chronic" forms. Then came the "Dauerstadium" of nephritis, described by Volhard and Fahr, as did the "chronic latent nephritis" of Addis. As ideas of immunology developed, beginning with Schick's landmark observations on streptococci, and then the work of von Pirquet on serum sickness in 1900-1910, immunological terms came into use: thus in the 1960s " (chronic) hypocomplementemic nephritis" made its appearance and by analogy from studies of experimental nephritis in animals, different patterns of deposition of immune reactants such as complement and immunoglobulin [Ig] were seen: the "lumpy bumpy" and "linear" deposits which Germuth and Dixon correlated to different routes of immunopathogenesis. Finally from the 1950s onwards terms based on the results of the new effective treatments treatment such as "corticosteroid-sensitive" and corticosteroid-resistant" nephritis appeared. About this time also the advent of renal biopsy showed the plasticity of renal histological appearances.

The result of all this was great confusion for pathologists, doctors – and not the least - patients. I have described the process above as though it was a conscious process of layering. However absolutely the reverse was true, and in 1968 when Jean Berger and his colleagues differentiated aggregates visible on fluorescent microscopy by immunoglobulin class, IgA as opposed to IgG, chaos reigned.

IIGANN VENNThe background to IgA nephropathy: an intersection of pathsTo place IgA nephropathy (Berger's disease) in context we must go back and trace the evolution of three layers of description in nephritis, which overlap as shown in the Venn diagram: the clinical syndrome of recurrent haematuria, the histological appearance of focal/mesangial nephritis, and the immunohistochemical appearance of predominant IgA deposition.

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