Leibniz-Inflammation Lectures

Chronic spontaneous urticaria–Autoimmunity as pathophysiological principle in this disease

Chronic urticaria is regarded as mast cell driven disease.
But why and how do the mast cells become activated?
What do we know so far? What have we learned from
recent therapeutic advances in this disease? We will
discuss current pathophysiological concepts and have a
brief look at other inflammatory diseases where similar
mechanisms could play a role.

Urticarial rash due to autoinflammation

Autoinflammatory diseases are mediated via
disturbances in innate immune signalling cascades.
Many of them present with chronic recurrent wheals
too. What are the cellular drivers of these diseases and
how are they activated? We will illustrate pathogenetic
insights, clinical clues and current treatment concepts.

Deep profiling of chronic inflammation by mass cytometry

By facilitating more than 40-dimensional cytometric analyses
on single-cell levels, mass cytometry permits assessing the
diversity of leukocytes and other cell types implicated in
the pathogenesis or reflecting the pathology of chronic
inflammation. The platform also serves for biosignature
discovery based on immune cells isolated from patients’
blood samples, facilitating the development of precision
medicine in chronic inflammatory diseases. I will discuss the
basics, capabilities, limitations and future promises of mass
cytometry, and the various techniques that together secure
superior quality of mass cytometry data required for successful
computational data mining of large data sets, selected data
analysis tools, and will highlight applications from my lab.

Implementation of mass cytometry in clinical practice

Rare diseases are clinically challenging since they are often
misdiagnosed and subsequently not properly treated. Here we
describe the opportunities of deep immune profiling by mass
and flow cytometry for the pathophysiologic characterization
of a patient with the unique combination of generalized
Lipodystrophy and severe intestinal inflammation, allowing
a tailored personalized endocrine and anti-inflammatory
therapy ultimately leading to stable clinical remission of the
patient.

Brain-targeting antibodies in encephalitis, psychosis and dementia

Autoimmune mechanisms causing dysfunction of the
brain are increasingly recognized in neurology and
psychiatry. Identification of pathogenic auto-antibodies
against neuronal tissue resulted in
unprecedented diagnostic and therapeutic
opportunities. Affected patients are at risk that such
treatable etiologies are overlooked as primary
neurodegenerative or psychiatric disorders. In some
patients the diagnosis can be made by detection of
specific auto-antibodies directed against neuronal or glial
surface proteins. The identification and recombinant
production of disease-defining human
monoclonal autoantibodies from these patients now
allow detailed analyses of the pathogenic effects, of
signaling cascades leading to neuropsychiatric
symptoms and potential triggers of autoimmunity.

Microbiota-reactive antibodies: protection against infections and contribution to autoimmunity

Chronic inflammatory processes are driven by
deregulated interactions between the host immune
system and the environment. This leads to the loss of
function of the targeted tissue. The recent technology
development revealed that commensal microbiota is
one of the crucial factors defining the fitness of the
host immune system. One of the major mechanisms of
microbiota control by immune system is production of
IgA at mucosal surfaces. Strikingly, not only IgA, but
also IgM and IgG can be found to be reactive
towards microbiota, implying their potential role in
host protection and, in some cases, in development of
autoimmunity. Mechanisms of the generation of such
antibodies, their specificity and potential contribution
to the development of tissue-restricted autoimmune
manifestations will be discussed.

Atopic Dermatitis

(clinical view)

• Age-dependent course of the disease
• Complications
• Treatment principles

Atopic Dermatitis
(mechanisms)

• Barrier
• Immunity
• Future therapeutic options

B cells in Chronic Inflammation

• How do B cells contribute to chronic inflammation?
• Are B cells always the bad guys?

B lineage cells as treatment targets in autoimmunity

•B cells in patients
•Pathogenesis
•B cells in RA, SLE and Vasculitis

Aufgezeichneter Vortrag

CNS and chronic inflammation

• Which mechanisms lead to neuronal damage during inflammation?
• Is there a “tissue memory” of inflammation in the CNS?

Dieser Vortrag musste leider ausfallen!

Current treatment options in multiple sclerosis

• Is MS now a treatable disease?
• Given that MS is also a neurodenegerative disorder, what can we do to prevent axonal damage and neuronal demise?
• Are there neuroprotective or even regenerative therapies on the horizon?

Targeting TNF to treat T cell-mediated responses upon transplantation

Chronic rheumatic diseases are associated with enhanced concentrations of proinflammatory cytokines (TNF, IL-6, IL-1b). In contrast to acute response, long exposure of the cells to such cytokines results in profound changes in their epigenetic state and responses to various stimuli. Thus, dissection of how cytokines act during acute and chronic inflammation represents a way for a development of new treatments of chronic inflmmatory diseases. Introduction of new immunosuppressive regimens has let to a dramatically improved short-term outcome and reduced incidence of acute rejection episodes after solid organ transplantation. However, established regimens cannot prevent early severe acute rejections in patients with a high proportion of preformed donor- or cross-reactive memory T cells. Thus, novel therapeutic approaches are needed.
First data from preclinical models and clinical trials indicate that TNF inhibition in conjunction with standard treatment approaches can control such T cell responses by either directly targeting memory T cells or boosting regulatory T cell function.

TNF in chronic rheumatic diseases

Chronic rheumatic diseases are associated with enhanced
concentrations of proinflammatory cytokines (TNF, IL-6,
IL-1b). In contrast to acute response, long exposure of the
cells to such cytokines results in profound changes in their
epigenetic state and responses to various stimuli. Thus,
dissection of how cytokines act during acute and chronic
inflammation represents a way for a development of new
treatments of chronic inflmmatory diseases.