[CIS PIDD] [cis-pidd] no CGD?

[Seppänen Mikko]

Dear Markus,

was chemotaxis tested (reduced?) and were neutrophils morphologically normal (hyposegmentation?), I am thinking of specific granule deficiency (SGD).

It is of course extremely rare (I think only 7 cases of mutated CEBPE + a few CEBPE neg cases reported in literature). However, the pathogens and findings make me (as well ) think mainly of neutrophils. However,  I am not aware of even animal KO data on reduced CD15 expression in CEBPE -/- nor CEBPE wt SGD (NIH's Steve Holland and/or J Lekström-Himes may know?).

Steve might be interested in this case, You have after all 2 affected patients. WES?

Hope this helps, good luck with the hunt! Hardly a coincidence, if You ask me...

mikko

__________________________________________________
Mikko Seppänen, MD, PhD, Docent (Associate professor/Senior Lecturer)
Specialist in Internal Medicine and Infectious Diseases
Senior Consultant, Physician in charge (PIDD)
EM(E)A Expert, PIDDs and Intravenous Immunoglobulin Therapy

Immunodeficiency Unit
Division of Infectious Diseases
Department of Medicine
Helsinki University Central Hospital
Hospital District of Helsinki and Uusimaa
Aurora Hospital, Ward 4-2 and Outpatient Clinic
P.O.Box 348
FI-00029 HUS, Helsinki
FINLAND
phone +358 9 47175923, fax +358 9 47175945
_________________________________________





Lähettäjä: Seidel Markus [mailto:markus.seidel at medunigraz.at]
Lähetetty: 16. huhtikuuta 2013 16:59
Vastaanottaja: CIS-PIDD
Aihe: [cis-pidd] no CGD?

Dear community,
I am asking for your highly appreciated distinct advice on the differential diagnostic options in a family with two boys who suffered from a very severe bacterial infection, suggestive of CGD but with repeatedly normal DHR tests; (for German see text below):
1)      The 8yo index patient of a bosnian, non-consanguineous family had a parasternal ulcerating tumor, diagnosed as posstraumatic mediastinitis with inflammatory pseudotumor with Fusobacterium nucleatum und Aggregatibacter actinomycetem comitans / DD Actonimykosis after having a bicycle accident 6 months previously and extraction of carious primary teeth a year before. He was treated with 3-4 months antibiotics and the lesion healed very well. All immunologic investigations including IgG, A, M, IgG subclasses, vaccination Abs, CH50,MBL,  T-, B, Nk cells, Phagocyte function (granulocyte and monocyte phagocytosis and oxidative burst [DHR; fluoresc.-labelled E.coli]) were normal, as was lmyphocyte function. Phagocyte numbers were normal, not suggestive of LAD.
2)      Currently, his 12yo brother is an inpatient at the surgical ICU for massive perforated phlegmonous appendicitis with intraabdominal abscesses, with need of repeated surgical revisions, responding moderately to antibiotics (6 different germs from various intraabdominal sites incl. Bacteroides and Steptococcus sp.), unfortunately the treatment included IVIG immediately before any diagnostic workup. All oft he above mentioned immunologic diagnostic tests were normal, inlcuding also CD16, CD32, CD64 CD15 on granulocytes and monocytes as well as CD11a,b, CD18 on granulocytes, only CD15s expression on granulocytes was reduced to 13% ; CD15 around 60% (will be repeated), however, neutrophil counts not elevated except during his ICU stay and Blood Group is B positive - not Bombay.
3)      Previous history as well as growth, healing of the umbilical cord, toothing, were normal; the mother complained recently of an annoying wound secretion in the region of her shoulder, otherwise normal family history, one healthy sister.

-) does anyone within the forum think these infections occur in immunocompetent individuals and are mere coincidence?
-) Are there any other tests required to exclude CGD? (It is difficult to ship specimen for this functional analyses to yield reliable results). Do genetics despite normal function test?
-) are there any other tests necessary to exclude neutrophil defects, given also the previously unremarkable history,
-) should we proceed to analyze TLR or other innate signalling pathways (any easily available routine tests we could perform? which lab would offer such non-routine tests?)
-) would you have other suggestions?

Thanks in advance for your input and comments,
Markus Seidel

Markus G. Seidel, M.D., Assoc.Prof.
Consultant| Dept.of Pediatric Hematology-Oncology | Univ.Clinics of Pediatric and Adolescent Medicine | Auenbruggerpl. 34/2 | A-8036 Graz | Austria | T. 0043 316 385 80215| F. 0043 316 385 13717 | Secr. 0043 316 385 13485 |
Coordinator of the Working Group for Pediatric Immunology of the Austrian Society of Pediatrics and Adolescent Medicine

________________________________
Attention:
This e-mail and any attachment is for authorised use by the intended recipient(s) only. It may contain proprietary, confidential and/or privileged information and should not be copied, disclosed, distributed, retained or used by any other party. If you are not an intended recipient please notify the sender immediately and delete this e-mail (including attachments and copies).


Der Indexpatient in einer aus Bosnien stammenden, nicht konsanguinen Familie ist ein 8-jähriger Junge, der im Vorjahr nach einem ca. 6 Monate zurückliegenden Fahrradsturz mit stumpfem Thoraxtrauma und einer ca. ein Jahr zurückliegenden Zahnsanierung (Entfernung kariöser Milchzahnreste, keine Zahnwechselproblematik) einen parasternalen ulcerierenden entzündlichen Tumor entwickelte, welcher später als "posttraumatische Mediastinitis durch Fusobacterium nucleatum und Aggregatibacter actinomycetem comitans" / DD Actonimykose diagnostiziert und behandelt wurde. Er sprach sehr gut auf Antibiotikatherapie an und wurde mehrere monate hindurch oral weiter behandelt bis zur praktischen Restitutio ad integrum.
Wir haben bei ihm damals nicht nur unsere "Stufe 1"-Abklärung (humoral inkl. CH50, zellulär, inkl. Lymphozytenstimulation) gemacht, sondern auch zweimalig die Granulozytenfunktion untersucht, die laut Labor lege artis mit fluoreszenzmarkierten E. coli (DHR; Phagozytose und oxidativer Burst) gemacht wurde, und bei Granulozyten beide Male jeweils 97-98% und bei Monos 87-92% ergab.
Aktuell ist der 12-jährige bruder auf der Intensivstation, weil er nach einer perforierten Appendix eine extreme eitrige Peritonitis mit intraabdominellen Abszessen hat, viele Drains hat und morgen reoperiert werden muss. Seine Keime sind E. coli, Bacteroides und Streptokokkus spp, wobei er relativ gut auf die erste OP und Antibiotikatherapie angesprochen hat, nur offenbar weiter sezerniert und sich möglicherweise wieder Eiter im Abd. Sammelt. Wir werden am Montag auch bei ihm eine immunologische Untersuchung starten, (leider rief man mich erst nach den ersten intensivmedizinisch verabreichten Immunglobulingaben).
Insgesamt ist das für mich hochverdächtig auf eine X-CGD, wobei die ja theoretisch durch die Vorbefunde vom Bruder (s.o.) ausgeschlossen ist. Es kann natürlich auch Zufall und Pech der zwei Brüder sein, jeder hat zuvor eine relativ unauffällige Anamnese, keine Krankenhausaufenthalte, keine entzündliche Darmerkrankung oder Fisteln; es gibt noch ein älteres Geschwisterkind, welches gesund ist (Geschlecht, Alter?). Die Mutter klagte anamnestisch über eine schlecht heilenden Hautläsion der Schulter mit Sekretion (Verlauf?).




---

The CIS-PIDD listserv is supported by:

[http://www.clinimmsoc.org/UserFiles/image/cis-pidd-list-logo_v1.jpg]
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org<https://cis.execinc.com/edibo/Signup> to join!

You are currently subscribed to cis-pidd as: mikko.seppanen at hus.fi<mailto:mikko.seppanen at hus.fi>.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183824751.2106f30c0050b88ca85ab6b5148641fa&n=T&l=cis-pidd&o=43200380

---
The CIS-PIDD listserv is supported by the Clinical Immunology Society
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org to join!

You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183939985.3ea13d40a15475ac00ebbd9cd8a37d6d&n=T&l=cis-pidd&o=43208500
or send a blank email to leave-43208500-183939985.3ea13d40a15475ac00ebbd9cd8a37d6d at lists.clinimmsoc.org
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/pipermail/pagid/attachments/20130417/47da42e7/attachment.html>